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  • 1.
    Abdurahman, Samir
    et al.
    Division of Clinical Microbiology, Department of Laboratory Medicine F68, Karolinska University Hospital, Stockholm, Sweden.
    Barqasho, Babilonia
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Nowak, Piotr
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Cuong, Do Duy
    Infectious Diseases Department, Bach Mai Hospital, Hanoi, Viet Nam .
    Amogné, Wondwossen
    Department of Medicine, Faculty of Medicine, University, Addis Abeba, Ethiopia .
    Larsson, Mattias
    Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden; Oxford University Clinical Research Unit (OUCRU), Hanoi, Viet Nam .
    Lindquist, Lars
    Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden .
    Marrone, Gaetano
    Division of Global Health (IHCAR), Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden .
    Sönnerborg, Anders
    Division of Clinical Microbiology, Department of Laboratory Medicine F68, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Pattern of microbial translocation in patients living with HIV-1 from Vietnam, Ethiopia and Sweden2014In: Journal of the International AIDS Society, E-ISSN 1758-2652, Vol. 17, p. 18841-Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The role of microbial translocation (MT) in HIV patients living with HIV from low- and middle-income countries (LMICs) is not fully known. The aim of this study is to investigate and compare the patterns of MT in patients from Vietnam, Ethiopia and Sweden.

    METHODS: Cross-sectional samples were obtained from treatment-naïve patients living with HIV-1 and healthy controls from Vietnam (n=83; n=46), Ethiopia (n=9492; n=50) and Sweden (n=51; n=19). Longitudinal samples were obtained from a subset of the Vietnamese (n=24) in whom antiretroviral therapy (ART) and tuberculostatics were given. Plasma lipopolysaccharide (LPS), sCD14 and anti-flagellin IgG were determined by the endpoint chromogenic Limulus Amebocyte Assay and enzyme-linked immunosorbent assay.

    RESULTS: All three biomarkers were significantly increased in patients living with HIV-1 from all countries as compared to controls. No differences were found between males and females. Vietnamese and Ethiopian patients had significantly higher levels of anti-flagellin IgG and LPS, as compared to Swedes. ART reduced these levels for the Vietnamese. Vietnamese patients given tuberculostatics at initiation of ART had significantly lower levels of anti-flagellin IgG and higher sCD14. The biomarkers were lower in Vietnamese who did not develop opportunistic infection.

    CONCLUSIONS: Higher MT is common in patients living with HIV compared to healthy individuals, and in patients from LMICs compared to patients from a high-income country. Treatment with tuberculostatics decreased MT while higher levels of MT are associated with a poorer clinical outcome.

  • 2.
    Abedi, Mohammad R.
    et al.
    Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
    Doverud, Ann-Charlotte
    Department of Laboratory Medicine, Section for Transfusion Medicine, Örebro University Hospital. Örebro, Sweden.
    Preparation and Pathogen Inactivation of Double Dose Buffy Coat Platelet Products using the INTERCEPT Blood System2012In: Journal of Visualized Experiments, E-ISSN 1940-087X, no 70, article id UNSP e4414Article in journal (Refereed)
    Abstract [en]

    Blood centers are faced with many challenges including maximizing production yield from the blood product donations they receive as well as ensuring the highest possible level of safety for transfusion patients, including protection from transfusion transmitted diseases. This must be accomplished in a fiscally responsible manner which minimizes operating expenses including consumables, equipment, waste, and personnel costs, among others.

    Several methods are available to produce platelet concentrates for transfusion. One of the most common is the buffy coat method in which a single therapeutic platelet unit (>= 2.0 x10(11) platelets per unit or per local regulations) is prepared by pooling the buffy coat layer from up to six whole blood donations. A procedure for producing "double dose" whole blood derived platelets has only recently been developed.

    Presented here is a novel method for preparing double dose whole blood derived platelet concentrates from pools of 7 buffy coats and subsequently treating the double dose units with the INTERCEPT Blood System for pathogen inactivation. INTERCEPT was developed to inactivate viruses, bacteria, parasites, and contaminating donor white cells which may be present in donated blood. Pairing INTERCEPT with the double dose buffy coat method by utilizing the INTERCEPT Processing Set with Dual Storage Containers (the "DS set"), allows blood centers to treat each of their double dose units in a single pathogen inactivation processing set, thereby maximizing patient safety while minimizing costs. The double dose buffy coat method requires fewer buffy coats and reduces the use of consumables by up to 50% (e.g. pooling sets, filter sets, platelet additive solution, and sterile connection wafers) compared to preparation and treatment of single dose buffy coat platelet units. Other cost savings include less waste, less equipment maintenance, lower power requirements, reduced personnel time, and lower collection cost compared to the apheresis technique.

  • 3. Abrahamsson, Thomas R.
    et al.
    Jakobsson, Ted
    Björkstén, Bengt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Oldaeus, Göran
    Jenmalm, Maria C.
    No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy2013In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 24, no 6, p. 556-561Article in journal (Refereed)
    Abstract [en]

    Background: Supplementation with the probioticLactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

    Objective: To evaluate whether perinatal and infant supplementation withL.reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.

    Methods: A randomized, placebo-controlled trial with oral supplementation withL.reuteriATCC 55730 (1x10(8)CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.govID NCT01285830).

    Results: The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.

    Conclusion: The effect ofL.reuteri on sensitization andIgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect ofL.reuteri on the immune system seems to be transient. Administration ofL.reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.

  • 4.
    Acevedo, Reinaldo
    et al.
    Biologic Evaluation Department, Finlay Institute of Vaccines, Havana, Cuba.
    Bai, Xilian
    Meningococcal Reference Unit, Public Health England, Manchester, UK.
    Borrow, Ray
    Meningococcal Reference Unit, Public Health England, Manchester, UK.
    Caugant, Dominique A.
    Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
    Carlos, Josefina
    Department of Pediatrics, College of Medicine, University of the East – Ramon Magsaysay Memorial Medical Center, Quezon City, Philippines.
    Ceyhan, Mehmet
    Faculty of Medicine, Department of Pediatric Infectious Diseases, Hacettepe University, Ankara, Turkey.
    Christensen, Hannah
    Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
    Climent, Yanet
    Biologic Evaluation Department, Finlay Institute of Vaccines, Havana, Cuba.
    De Wals, Philippe
    Department of Social and Preventive Medicine, Laval University, Quebec City QC, Canada.
    Dinleyici, Ener Cagri
    Department of Paediatrics, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey.
    Echaniz-Aviles, Gabriela
    Center for Research on Infectious Diseases, Instituto Nacional de Salud Pública, Cuernavaca, México.
    Hakawi, Ahmed
    Infectious Diseases Control, Ministry of Health, Riyadh, Saudi Arabia.
    Kamiya, Hajime
    Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan.
    Karachaliou, Andromachi
    Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    Lucidarme, Jay
    Meningococcal Reference Unit, Public Health England, Manchester, UK.
    Meiring, Susan
    Division of Public Health Surveillance and Response, National Institute for Communicable Diseases, Johannesburg, South Africa.
    Mironov, Konstantin
    Central Research Institute of Epidemiology, Moscow, Russian Federation.
    Safadi, Marco A. P.
    Department of Pediatrics, FCM Santa Casa de São Paulo School of Medical Sciences, São Paulo, Brazil.
    Shao, Zhujun
    National Institute for Communicable Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China.
    Smith, Vinny
    Meningitis Research Foundation, Bristol, UK.
    Steffen, Robert
    Department of Epidemiology and Prevention of Infectious Diseases, WHO Collaborating Centre for Travellers’ Health, University of Zurich, Zurich, Switzerland.
    Stenmark, Bianca
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Taha, Muhamed-Kheir
    Institut Pasteur, National Reference Centre for Meningococci, Paris, France.
    Trotter, Caroline
    Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
    Vazquez, Julio A.
    National Centre of Microbiology, Institute of Health Carlos III, Madrid, Spain.
    Zhu, Bingqing
    National Institute for Communicable Disease Control and Prevention, Chinese Centre for Disease Control and Prevention, Beijing, China.
    The Global Meningococcal Initiative meeting on prevention of meningococcal disease worldwide: Epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations2019In: Expert Review of Vaccines, ISSN 1476-0584, E-ISSN 1744-8395, Vol. 18, no 1, p. 15-30Article, review/survey (Refereed)
    Abstract [en]

    Introduction: The 2018 Global Meningococcal Initiative (GMI) meeting focused on evolving invasive meningococcal disease (IMD) epidemiology, surveillance, and protection strategies worldwide, with emphasis on emerging antibiotic resistance and protection of high-risk populations. The GMI is comprised of a multidisciplinary group of scientists and clinicians representing institutions from several continents.

    Areas covered: Given that the incidence and prevalence of IMD continually varies both geographically and temporally, and surveillance systems differ worldwide, the true burden of IMD remains unknown. Genomic alterations may increase the epidemic potential of meningococcal strains. Vaccination and (to a lesser extent) antimicrobial prophylaxis are the mainstays of IMD prevention. Experiences from across the globe advocate the use of conjugate vaccines, with promising evidence growing for protein vaccines. Multivalent vaccines can broaden protection against IMD. Application of protection strategies to high-risk groups, including individuals with asplenia, complement deficiencies and human immunodeficiency virus, laboratory workers, persons receiving eculizumab, and men who have sex with men, as well as attendees at mass gatherings, may prevent outbreaks. There was, however, evidence that reduced susceptibility to antibiotics was increasing worldwide.

    Expert commentary: The current GMI global recommendations were reinforced, with several other global initiatives underway to support IMD protection and prevention.

  • 5.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Hematology, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Clinical Research Centre, Örebro University Hospital, Örebro, Sweden.
    Persson, Lennart
    Örebro University Hospital. Department of Infectious diseases, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Tidefelt, Ulf
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious diseases & Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 6, p. 539-544Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  • 6.
    Alijagic, Andi
    et al.
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Benada, Oldřich
    Institute of Microbiology of The Czech Academy of Sciences, Prague, Czechia.
    Kofroňová, Olga
    Institute of Microbiology of The Czech Academy of Sciences, Prague, Czechia.
    Cigna, Diego
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Pinsino, Annalisa
    Istituto per la Ricerca e l'Innovazione Biomedica (IRIB), Consiglio Nazionale delle Ricerche, Palermo, Italy.
    Sea Urchin Extracellular Proteins Design a Complex Protein Corona on Titanium Dioxide Nanoparticle Surface Influencing Immune Cell Behavior2019In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 10, article id 2261Article in journal (Refereed)
    Abstract [en]

    Extensive exploitation of titanium dioxide nanoparticles (TiO2NPs) augments rapid release into the marine environment. When in contact with the body fluids of marine invertebrates, TiO2NPs undergo a transformation and adhere various organic molecules that shape a complex protein corona prior to contacting cells and tissues. To elucidate the potential extracellular signals that may be involved in the particle recognition by immune cells of the sea urchin Paracentrotus lividus, we investigated the behavior of TiO2NPs in contact with extracellular proteins in vitro. Our findings indicate that TiO2NPs are able to interact with sea urchin proteins in both cell-free and cell-conditioned media. The two-dimensional proteome analysis of the protein corona bound to TiO2NP revealed that negatively charged proteins bound preferentially to the particles. The main constituents shaping the sea urchin cell-conditioned TiO2NP protein corona were proteins involved in cellular adhesion (Pl-toposome, Pl-galectin-8, Pl-nectin) and cytoskeletal organization (actin and tubulin). Immune cells (phagocytes) aggregated TiO2NPs on the outer cell surface and within well-organized vesicles without eliciting harmful effects on the biological activities of the cells. Cells showed an active metabolism, no oxidative stress or caspase activation. These results provide a new level of understanding of the extracellular proteins involved in the immune-TiO2NP recognition and interaction in vitro, confirming that primary immune cell cultures from P. lividus can be an optional model for swift and efficient immune-toxicological investigations. 

  • 7.
    Alijagic, Andi
    et al.
    Consiglio Nazionale delle Ricerche, Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), Palermo, Italy.
    Bonura, Angela
    Consiglio Nazionale delle Ricerche, Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), Palermo, Italy.
    Barbero, Francesco
    Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, Barcelona, Spain.
    Puntes, Victor F.
    Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and BIST, Campus UAB, Bellaterra, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain; Vall d Hebron Institut de Recerca (VHIR), Barcelona, Spain.
    Gervasi, Fransesco
    Specialistic Oncology Laboratory Unit, ARNAS Hospitals Civico Di Cristina e Benfratelli, Palermo, Italy.
    Pinsino, Annalisa
    Consiglio Nazionale delle Ricerche, Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), Palermo, Italy.
    Immunomodulatory Function of Polyvinylpyrrolidone (PVP)-Functionalized Gold Nanoparticles in Vibrio-Stimulated Sea Urchin Immune Cells2021In: Nanomaterials, E-ISSN 2079-4991, Vol. 11, no 10, article id 2646Article in journal (Refereed)
    Abstract [en]

    We investigated the role of the gold nanoparticles functionalized with polyvinylpyrrolidone (PVP–AuNPs) on the innate immune response against an acute infection caused by Vibrio anguillarum in an in vitro immunological nonmammalian next-generation model, the sea urchin Paracentrotus lividus. To profile the immunomodulatory function of PVP–AuNPs (0.1 μg mL−1) in sea urchin immune cells stimulated by Vibrio (10 μg mL−1) for 3 h, we focused on the baseline immunological state of the donor, and we analysed the topography, cellular metabolism, and expression of human cell surface antigens of the exposed cells, as well as the signalling leading the interaction between PVP–AuNPs and the Vibrio-stimulated cells. PVP–AuNPs are not able to silence the inflammatory signalling (TLR4/p38MAPK/NF-κB signalling) that involves the whole population of P. lividus immune cells exposed to Vibrio. However, our findings emphasise the ability of PVP–AuNPs to stimulate a subset of rare cells (defined here as Group 3) that express CD45 and CD14 antigens on their surface, which are known to be involved in immune cell maturation and macrophage activation in humans. Our evidence on how PVP–AuNPs may stimulate sea urchin immune cells represents an important starting point for planning new research work on the topic. 

  • 8.
    Alijagic, Andi
    et al.
    Örebro University, School of Science and Technology. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hedbrant, Alexander
    Örebro University, School of Medical Sciences. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Persson, Alexander
    Örebro University, School of Medical Sciences. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Larsson, Maria
    Örebro University, School of Science and Technology.
    Engwall, Magnus
    Örebro University, School of Science and Technology.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    NLRP3 inflammasome as a sensor of micro- and nanoplastics immunotoxicity2023In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 14, article id 1178434Article, review/survey (Refereed)
    Abstract [en]

    Micro- and nanoplastics (MNPs) are emerging pollutants with scarcely investigated effects on human innate immunity. If they follow a similar course of action as other, more thoroughly investigated particulates, MNPs may penetrate epithelial barriers, potentially triggering a cascade of signaling events leading to cell damage and inflammation. Inflammasomes are intracellular multiprotein complexes and stimulus-induced sensors critical for mounting inflammatory responses upon recognition of pathogen- or damage-associated molecular patterns. Among these, the NLRP3 inflammasome is the most studied in terms of activation via particulates. However, studies delineating the ability of MNPs to affect NLRP3 inflammasome activation are still rare. In this review, we address the issue of MNPs source and fate, highlight the main concepts of inflammasome activation via particulates, and explore recent advances in using inflammasome activation for assessment of MNP immunotoxicity. We also discuss the impact of co-exposure and MNP complex chemistry in potential inflammasome activation. Development of robust biological sensors is crucial in order to maximize global efforts to effectively address and mitigate risks that MNPs pose for human health.

  • 9.
    Almroth, G.
    et al.
    Department of Nephrology, Institution of medicine and health sciences, Linköping University, Linköping, Sweden.
    Lönn, Johanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Uhlin, F.
    Department of Nephrology, Institution of medicine and health sciences, Linköping University, Linköping, Sweden.
    Brudin, L.
    Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Department of Physiology, County Hospital, Kalmar, Sweden.
    Andersson, B.
    Department of Clinical Immunology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Hahn-Zoric, M.
    Department of Clinical Immunology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Sclerostin, TNF-alpha and Interleukin-18 Correlate and are Together with Klotho Related to Other Growth Factors and Cytokines in Haemodialysis Patients2016In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 83, no 1, p. 58-63Article in journal (Refereed)
    Abstract [en]

    Patients with chronic renal failure are known to have renal osteodystrophy (bone disease) and increased calcification of vessels. A new marker of bone disease, sclerostin, the two pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18), and the fibroblast growth factor-23 (FGF-23) receptor-associated marker Klotho were tested in 84 haemodialysis (HD) patients and in healthy controls. The patients had significantly higher levels of the three former markers than of the controls while Klotho was significantly higher in the controls. Low level, but significant, correlations were observed in the patient group when the levels of these four markers were compared to each other and to those of 5 cytokines and growth factors tested earlier; high-sensitive CRP (hsCRP), interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor-23 (FGF-23) and soluble urokinase plasminogen activator (suPAR). Ln sclerostin correlated positively to Ln hsTNF-alpha, Ln HGF and Ln suPAR. Ln hsTNF-alpha correlated positively to Ln sclerostin, Ln hsCRP, Ln IL-6, Ln FGF-23, Ln suPAR and Ln IL-18. Ln IL-18 correlated positively to Ln suPAR and Ln TNF-alpha. Ln Klotho correlated negatively to Ln hsCRP but did not correlate to Ln FGF-23. The markers studied here may be involved in the calcification of vessels seen in HD patients due to a combination of inflammation and bone disease. The mechanisms are still not fully known but may be of importance for future therapeutic possibilities in this group of patients.

  • 10.
    Almroth, G.
    et al.
    Departments of Nephrology, Linköping University Hospital, Linköping, Sweden; Department of Medicine and Health Sciences, Linköping University Hospital, Linköping, Sweden.
    Lönn, Johanna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. PEAS Institute, Linköping, Sweden.
    Uhlin, F.
    Departments of Nephrology, Linköping University Hospital, Linköping, Sweden; Department of Medicine and Health Sciences, Linköping University Hospital, Linköping, Sweden.
    Nayeri, F.
    PEAS Institute, Linköping, Sweden; Division of Infectious diseases, Linköping University Hospital, Linköping, Sweden.
    Brudin, L.
    Department of Medicine and Health Sciences, Linköping University Hospital, Linköping, Sweden; Department of Physiology, Kalmar County Hospital, Kalmar, Sweden.
    Andersson, B.
    Department of Clinical Immunology, Sahlgren’s University Hospital, Gothenburg, Sweden.
    Hahn-Zoric, M.
    Department of Clinical Immunology, Sahlgren’s University Hospital, Gothenburg, Sweden.
    Fibroblast growth factor 23, hepatocyte growth factor, interleukin-6, high-sensitivity c-reactive protein and soluble urokinase plasminogen activator receptor: Inflammation markers in chronic haemodialysis patients?2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 3, p. 285-290Article in journal (Refereed)
    Abstract [en]

    Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

  • 11. Amoudruz, Petra
    et al.
    Holmlund, Ulrika
    Schollin, Jens
    Örebro University, School of Health and Medical Sciences.
    Sverremark-Ekström, Eva
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Maternal country of birth and previous pregnancies are associated with breast milk characteristics2009In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 20, no 1, p. 19-29Article in journal (Refereed)
    Abstract [en]

    Populations in high infectious exposure countries are at low risk of some immune-mediated diseases such as Crohn's disease and allergy. This low risk is maintained upon immigration to an industrialized country, but the offspring of such immigrants have a higher immune-mediated disease risk than the indigenous population. We hypothesize that early life exposures in a developing country shape the maternal immune system, which could have implications for the offspring born in a developed country with a low infectious load. The aim of this study was to investigate if exposures in childhood (indicated by country of origin) and subsequent exposures influence immunologic characteristics relevant to stimulation of offspring. Breast milk components among 64 mothers resident in Sweden, 32 of whom immigrated from a developing country, were examined using the ELISA and Cytometric Bead Array methods. Immigrants from a developing country had statistically significantly higher levels of breast milk interleukin-6 (IL-6), IL-8 and transforming growth factor-beta1. A larger number of previous pregnancies were associated with down-regulation of several substances, statistically significant for soluble CD14 and IL-8. The results suggest that maternal country of birth may influence adult immune characteristics, potentially relevant to disease risk in offspring. Such a mechanism may explain the higher immune-mediated disease risk among children of migrants from a developing to developed country. Older siblings may influence disease risk through the action of previous pregnancies on maternal immune characteristics.

  • 12.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    CHIMERIC MOMP ANTIGEN2015Patent (Other (popular science, discussion, etc.))
    Download full text (pdf)
    Patent
  • 13.
    Andersson, Sören
    et al.
    Örebro University, School of Medical Sciences. Folkhälsomyndigheten, Public Health Agency of Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Chimeric MOMP antigen2014Patent (Other (popular science, discussion, etc.))
    Abstract [en]

    The present invention regards polypeptides capable of eliciting an immunological response that is protective against Chlamydia trachomatis. The polypeptide comprises a first amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 1 and a second amino acid sequence which has at least 90% homology with the amino acid sequence according to SEQ ID NO: 2. Furthermore, production of these polypeptides and pharmaceutical compositions comprising them are also provided.

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  • 14.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Medical Sciences. iRiSC-Inflammatory Response and Infection Susceptibility Centre.
    Kelly, Anne
    iRiSC-Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Karolinska University Hospital, Solna, Stockholm, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. iRiSC-Inflammatory Response and Infection Susceptibility Centre.
    Demirel, Isak
    Örebro University, School of Medical Sciences. iRiSC-Inflammatory Response and Infection Susceptibility Centre.
    Fredlund, Hans
    iRiSC-Inflammatory Response and Infection Susceptibility Centre.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. iRiSC-Inflammatory Response and Infection Susceptibility Centre.
    Persson, Alexander
    Örebro University, School of Medical Sciences. iRiSC-Inflammatory Response and Infection Susceptibility Centre.
    Neisseria meningitidis-Induced Caspase-1 Activation in Human Innate Immune Cells Is LOS-Dependent2019In: Journal of Immunology Research, ISSN 2314-8861, E-ISSN 2314-7156, article id 6193186Article in journal (Refereed)
    Abstract [en]

    Meningococcal disease such as sepsis and meningitidis is hallmarked by an excessive inflammatory response. The causative agent, Neisseria meningitidis, expresses the endotoxin lipooligosaccharide (LOS) that is responsible for activation of immune cells and the release of proinflammatory cytokines. One of the most potent proinflammatory cytokines, interleukin-1 (IL-1), is activated following caspase-1 activity in the intracellular multiprotein complex called inflammasome. Inflammasomes are activated by a number of microbial factors as well as danger molecules by a two-step mechanismpriming and licensing of inflammasome activationbut there are no data available regarding a role for inflammasome activation in meningococcal disease. The aim of this study was to investigate if N. meningitidis activates the inflammasome and, if so, the role of bacterial LOS in this activation. Cells were subjected to N. meningitidis, both wild-type (FAM20) and its LOS-deficient mutant (lpxA), and priming as well as licensing of inflammasome activation was investigated. The wild-type LOS-expressing parental FAM20 serogroup C N. meningitidis (FAM20) strain significantly enhanced the caspase-1 activity in human neutrophils and monocytes, whereas lpxA was unable to induce caspase-1 activity as well as to induce IL-1 release. While the lpxA mutant induced a priming response, measured as increased expression of NLRP3 and IL1B, the LOS-expressing FAM20 further increased this priming. We conclude that although non-LOS components of N. meningitidis contribute to the priming of the inflammasome activity, LOS per se is to be considered as the central component of N. meningitidis virulence, responsible for both priming and licensing of inflammasome activation.

  • 15.
    Asfaw Idosa, Berhane
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Sahdo, Berolla
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Balcha, Ermias
    Department of Clinical Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Swedenital, Örebro, Sweden.
    Kelly, Anne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Clinical Medicine.
    C10X polymorphism in the CARD8 gene is associated with bacteraemia2014In: Immunity, inflammation and disease, E-ISSN 2050-4527, Vol. 2, no 1, p. 13-20Article in journal (Refereed)
    Abstract [en]

    The NLRP3 inflammasome is an intracellular multi-protein complex that triggers caspase-1 mediated maturation of interleukin-1β (IL-1β); one of the most potent mediators of inflammation and a major cytokine produced during severe infections, like sepsis. However, the excessive cytokine levels seem to stage for tissue injury and organ failure, and high levels of IL-1β correlates with severity and mortality of sepsis. Instead, recent data suggest caspase-1 to function as a guardian against severe infections. CARD8 has been implied to regulate the synthesis of IL-1β via interaction to caspase-1. In recent years, polymorphism of CARD8 (C10X) per se or in combination with NLRP3 (Q705K) has been implicated with increased risk of inflammation. The aim was to investigate the correlation of these polymorphisms with severe blood stream infection. Human DNA was extracted from blood culture bottles that were found to be positive for microbial growth (i.e. patients with bacteraemia). Polymorphisms Q705K in the NLRP3 gene and C10X in the CARD8 gene were genotyped using TaqMan genotyping assay. The results were compared to healthy controls and to samples from patients with negative cultures. The polymorphism C10X was significantly over-represented among patients with bacteraemia as compared to healthy controls, whereas patients with negative blood culture were not associated with a higher prevalence. No association was observed with polymorphism Q705K of NLRP3 in either group of patients. Patients carrying polymorphism C10X in the CARD8 gene are at increased risk of developing bacteraemia and severe inflammation.

  • 16.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Jaafar, Rita
    Örebro University, School of Medical Sciences.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Ljunberg, Karl
    Eurocine Vaccines AB, Solna, Sweden.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Design, rescue, and characterization of Langat virus infectious clone by next generation sequencing2023Conference paper (Other academic)
    Abstract [en]

    Tick-borne encephalitis (TBE) is one of the most important tick-transmitted diseases in Europe and Asia. TBE virus (TBEV) infections cause mild flu-like symptoms that may lead to severe neurological disorders. The incidence of TBE cases in Sweden has increase remarkably over the last decades. There is no specific antiviral treatment available against TBEV and vaccination remains the best protective measure. The currently available TBE vaccines require repeated injections for long-term immunity and vaccine failure can occur in some patients due to poor immunogenicity in the elderly. 

    Live attenuated viral vaccines are known to provide long-term immunity with fewer doses whereas the commercial TBE vaccines are based on single surface protein of the virus. We aim to develop a modified live attenuated TBE vaccine based on Langat virus (LGTV). LGTV is a naturally attenuated strain of TBEV. We aim to weaken the virus further by introducing modifications within LGTV genome. In this study we have successfully designed and rescued infectious clones of LGTV using RNA and DNA based strategies. We passaged these infections clones in cell culture and performed next generation sequencing to study similarity of rescued viruses to the parental LGTV sequence and their stability in cell culture. 

    Note: Visit my poster to discuss the results of next generation sequencing analysis and rescue strategies for LGTV infectious clones. 

  • 17.
    Asghar, Naveed
    et al.
    Örebro University, School of Medical Sciences.
    Melik, Wessam
    Örebro University, School of Medical Sciences.
    Paulsen, Katrine M.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Pedersen, Benedikte N.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Bø-Granquist, Erik G.
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Vikse, Rose
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Stuen, Snorre
    Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Sandnes, Norway.
    Andersson, Sören
    Folkhälsomyndigheten, Public Health Agency of Sweden, Solna, Sweden.
    Strid, Åke
    Örebro University, School of Science and Technology.
    Andreassen, Åshild K.
    Department of Virology, Division for Infection Control, Norwegian Institute of Public Health, Oslo, Norway.
    Johansson, Magnus
    Örebro University, School of Medical Sciences.
    Transient Expression of Flavivirus Structural Proteins in Nicotiana benthamiana 2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 10, article id 1667Article in journal (Refereed)
    Abstract [en]

    Flaviviruses are a threat to public health and can cause major disease outbreaks. Tick-borne encephalitis (TBE) is caused by a flavivirus, and it is one of the most important causes of viral encephalitis in Europe and is on the rise in Sweden. As there is no antiviral treatment availa-ble, vaccination remains the best protective measure against TBE. Currently available TBE vaccines are based on formalin-inactivated virus produced in cell culture. These vaccines must be delivered by intramuscular injection, have a burdensome immunization schedule, and may exhibit vaccine failure in certain populations. This project aimed to develop an edible TBE vaccine to trigger a stronger immune response through oral delivery of viral antigens to mucosal surfaces. We demonstrated successful expression and post-translational processing of flavivirus structural pro-teins which then self-assembled to form virus-like particles in Nicotiana benthamiana. We performed oral toxicity tests in mice using various plant species as potential bioreactors and evaluated the immunogenicity of the resulting edible vaccine candidate. Mice immunized with the edible vaccine candidate did not survive challenge with TBE virus. Interestingly, immunization of female mice with a commercial TBE vaccine can protect their offspring against TBE virus infection. 

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  • 18.
    Assadi, G.
    et al.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Saleh, R.
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Hadizadeh, F.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Vesterlund, L.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Bonfiglio, F.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Törkvist, L.
    Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden.
    Eriksson, A. S.
    Gatroenterology Unit, Department of Internal Medicine, Sahlgren's University Hospital/Östra, Göteborg, Sweden.
    Harris, H. E.
    Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Sundberg, E.
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    D'Amato, M.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioCruces Health Research Institute and IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    LACC1 polymorphisms in inflammatory bowel disease and juvenile idiopathic arthritis2016In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 17, no 4, p. 261-264Article in journal (Refereed)
    Abstract [en]

    The function of the Laccase domain-containing 1 (LACC1) gene is unknown, but genetic variation at this locus has been reported to consistently affect the risk of Crohn's disease (CD) and leprosy. Recently, a LACC1 missense mutation was found in patients suffering from monogenic forms of CD, but also systemic juvenile idiopathic arthritis. We tested the hypothesis that LACC1 single nucleotide polymorphisms (SNPs), in addition to CD, are associated with juvenile idiopathic arthritis (JIA, non-systemic), and another major form of inflammatory bowel disease, ulcerative colitis (UC). We selected 11 LACC1 tagging SNPs, and tested their effect on disease risk in 3855 Swedish individuals from three case-control cohorts of CD, UC and JIA. We detected false discovery rate corrected significant associations with individual markers in all three cohorts, thereby expanding previous results for CD also to UC and JIA. LACC1's link to several inflammatory diseases suggests a key role in the human immune system and justifies further characterization of its function(s).

  • 19.
    Athlin, Simon
    et al.
    Örebro University Hospital.
    Kaltoft, Margit
    Statens Serum Institut, Copenhagen, Denmark.
    Slotved, Hans-Christian
    Statens Serum Institut, Copenhagen, Denmark.
    Herrmann, Björn
    Uppsala University, Uppsala, Sweden.
    Holmberg, Hans
    Örebro University Hospital.
    Konradsen, Helle Bossen
    Statens Serum Institut, Copenhagen, Denmark.
    Strålin, Kristoffer
    Örebro University Hospital, Örebro, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Association between serotype-specific antibody response and serotype characteristics in patients with pneumococcal pneumonia, with special reference to degree of encapsulation and invasive potential2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 11, p. 1541-1549Article in journal (Refereed)
    Abstract [en]

    We studied the immunoglobulin (Ig) response to causative serotype-specific capsular polysaccharides in adult pneumococcal pneumonia patients. The serotypes were grouped according to their degree of encapsulation and invasive potential. Seventy patients with pneumococcal pneumonia, 20 of whom were bacteremic, were prospectively studied. All pneumococcal isolates from the patients were serotyped, and the Ig titers to the homologous serotype were determined in acute- and convalescent-phase sera using a serotype-specific enzyme-linked immunosorbent assay. The Ig titers were lower in bacteremic cases than in nonbacteremic cases (P < 0.042). The Ig titer ratio (convalescent/acute titer) was ≥2 in 33 patients, 1 to 1.99 in 20 patients, and <1 in 17 patients. Patients ≥65 years old had a lower median Ig titer ratio than did younger patients (P < 0.031). The patients with serotypes with a thin capsule (1, 4, 7F, 9N, 9V, and 14) and medium/high invasive potential (1, 4, 7F, 9N, 9V, 14, and 18C) had higher Ig titer ratios than did patients with serotypes with a thick capsule (3, 6B, 11A, 18C, 19A, 19F, and 23F) and low invasive potential (3, 6B, 19A, 19F, and 23F) (P < 0.05 for both comparisons after adjustment for age). Ig titer ratios of <1 were predominantly noted in patients with serotypes with a thick capsule. In 8 patients with pneumococcal DNA detected in plasma, the three patients with the highest DNA load had the lowest Ig titer ratios. In conclusion, a high antibody response was associated with serotypes with a thin capsule and medium/high invasive potential, although a low antibody response was associated with serotypes with a thick capsule and a high pneumococcal plasma load.

  • 20.
    Bang, Charlotte Sahlberg
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kruse, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Önnberg, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Dept Lab Med, Örebro University Hospital, Örebro, Sweden.
    Persson, Katarina
    Örebro University, School of Medicine, Örebro University, Sweden.
    Multiresistant uropathogenic extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are susceptible to the carbon monoxide releasing molecule-2 (CORM-2).2014In: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 66, p. 29-35Article in journal (Refereed)
    Abstract [en]

    Carbon monoxide (CO) releasing molecules (CO-RMs) have been shown to inhibit growth of commensal Escherichia coli (E. coli). In the present study we examined the effect of CORM-2 on uropathogenic E. coli (UPEC) that produces extended-spectrum β-lactamase (ESBL). Viability experiments showed that CORM-2 inhibited the growth of several different ESBL-producing UPEC isolates and that 500 μM CORM-2 had a bactericidal effect within 4 h. The bactericidal effect of CORM-2 was significantly more pronounced than the effect of the antibiotic nitrofurantoin. CORM-2 demonstrated a low level of cytotoxicity in eukaryotic cells (human bladder epithelial cell line 5637) at the concentrations and time-points where the antibacterial effect was obtained. Real-time RT-PCR studies of different virulence genes showed that the expression of capsule group II kpsMT II and serum resistance traT was reduced and that some genes encoding iron acquisition systems were altered by CORM-2. Our results demonstrate that CORM-2 has a fast bactericidal effect against multiresistant ESBL-producing UPEC isolates, and also identify some putative UPEC virulence factors as targets for CORM-2. CO-RMs may be candidate drugs for further studies in the field of finding new therapeutic approaches for treatment of uropathogenic ESBLproducing E. coli.

  • 21.
    Barcenilla, Hugo
    et al.
    Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
    Pihl, Mikael
    Core Facility, Flow Cytometry Unit, Linköping University, Linköping, Sweden.
    Wahlberg, Jeanette
    Örebro University, School of Medical Sciences. Department of Health, Medicine and Caring Sciences (HMV), Linköping University, Linköping, Sweden; Division of Diagnostics and Specialist Medicine and Faculty of Health Sciences, Örebro University, Örebro, Sweden.
    Ludvigsson, Johnny
    Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Division of Pediatrics, Crown Princess Victoria Children's Hospital, Linköping, Sweden.
    Casas, Rosaura
    Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
    Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes2021In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 797172Article in journal (Refereed)
    Abstract [en]

    Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes. 

  • 22.
    Bazargani, Farhan
    et al.
    Department of Anatomy and Cell Biology, Göteborg University, Göteborg, Sweden.
    Rother, R. P.
    Alexion Pharmaceuticals, Cheshire, CT, United States.
    Braide, M.
    Department of Anatomy and Cell Biology, Göteborg University, Göteborg, Sweden.
    The roles of complement factor C5a and CINC-1 in glucose transport, ultrafiltration, and neutrophil recruitment during peritoneal dialysis2006In: Peritoneal Dialysis International, ISSN 0896-8608, E-ISSN 1718-4304, Vol. 26, no 6, p. 688-696Article in journal (Refereed)
    Abstract [en]

    Background: In a recent experimental study, we showed that low molecular weight heparin improved ultrafiltration and blocked complement activation and coagulation in a single peritoneal dialysis (PD) dwell.

    Objective: The aim of the present study was to evaluate the possible contribution of the complement factor C5a and the potential interactions between C5a, the coagulation system, and cytokines of the interleukin (IL)-8 family (cytokine-induced neutrophil chemoattractant; CINC-1).

    Methods: Nonuremic rats were exposed through an in-dwelling catheter to a single dose of 20 mL glucose- (2.5%) based fifter-sterilized PD fluid, with or without the addition of anti-rat CS antibody. The dwell fluid was analyzed 2 and 4 hours later concerning activation of the coagulation cascades, neutrophil recruitment, ultrafiltration volume; CINC-1, glucose, urea, and histamine concentrations; and ex vivo intraperitoneal chemotactic activity. 

    Results: The numbers of neutrophils and levels of thrombin-antithrombin complex (TAT) and CINC-1 increased significantly during the PD dwell. C5 blockade significantly reduced the levels of TAT and increased the ultrafiltration volumes at 2 hours. Glucose concentrations were significantly positively correlated to ultrafiltration volumes.

    Conclusions: Blockade of C5 Leads to an increase in ultrafiltration, probably by a mechanism that involves a reduction in glucose transport. This effect may form a basis for improving PD efficiency in situations where high glucose transport limits ultrafiltration. Mechanisms connected to complement activation during PD may involve coagulation. Further studies of the intraperitoneal cascade systems under conditions of PD are indicated.

  • 23.
    Bengtsson, Torbjörn
    et al.
    Örebro University, School of Medical Sciences.
    Zhang, Boxi
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Selegård, Robert
    Örebro University, School of Medical Sciences. Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Wiman, Emanuel
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Dual action of bacteriocin PLNC8 alpha beta through inhibition of Porphyromonas gingivalis infection and promotion of cell proliferation2017In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 5, article id ftx064Article in journal (Refereed)
    Abstract [en]

    Periodontitis is a chronic inflammatory disease that is characterised by accumulation of pathogenic bacteria, including Porphyromonas gingivalis, in periodontal pockets. The lack of effective treatments has emphasised in an intense search for alternative methods to prevent bacterial colonisation and disease progression. Bacteriocins are bacterially produced antimicrobial peptides gaining increased consideration as alternatives to traditional antibiotics. We show rapid permeabilisation and aggregation of P. gingivalis by the two-peptide bacteriocin PLNC8 alpha beta. In a cell culture model, P. gingivalis was cytotoxic against gingival fibroblasts. The proteome profile of fibroblasts is severely affected by P. gingivalis, including induction of the ubiquitin-proteasome pathway. PLNC8 alpha beta enhanced the expression of growth factors and promoted cell proliferation, and suppressed proteins associated with apoptosis. PLNC8 alpha beta efficiently counteracted P. gingivalis-mediated cytotoxicity, increased expression of a large number of proteins and restored the levels of inflammatory mediators. In conclusion, we show that bacteriocin PLNC8 alpha beta displays dual effects by acting as a potent antimicrobial agent killing P. gingivalis and as a stimulatory factor promoting cell proliferation. We suggest preventive and therapeutical applications of PLNC8 alpha beta in periodontitis to supplement the host immune defence against P. gingivalis infection and support wound healing processes.

  • 24.
    Bergström, Ida
    et al.
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Lundberg, Anna K.
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Jönsson, Simon
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. IRiSC - Inflammatory Response and Infection Susceptibility Centre.
    Ernerudh, Jan
    Department of Clinical Immunology and Transfusion Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Jonasson, Lena
    Department of Medical and Health Sciences, Division of Cardiovascular Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Annexin A1 in blood mononuclear cells from patients with coronary artery disease: Its association with inflammatory status and glucocorticoid sensitivity2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174177Article in journal (Refereed)
    Abstract [en]

    Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of glucocorticoid actions. In atherosclerotic tissue, increased expression of AnxA1 has been associated with protective plaque-stabilizing effects. Here, we investigated the expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease (CAD). Blood was collected from 57 patients with stable CAD (SCAD) and 41 healthy controls. We also included a minor group (n = 10) with acute coronary syndrome (ACS). AnxA1 mRNA was measured in PBMCs. Expression of AnxA1 protein (total and surface-bound) and glucocorticoid receptors (GR) were detected in PBMC subsets by flow cytometry. Also, salivary cortisol, interleukin(IL)-6 and IL-10 in plasma, and LPS-induced cytokine secretion from PBMCs, with or without dexamethasone, were assessed. AnxA1 mRNA was found to be slightly increased in PBMCs from SCAD patients compared with controls. However, protein expression of AnxA1 or GRs in PBMC subsets did not differ between SCAD patients and controls, despite SCAD patients showing a more proinflammatory cytokine profile ex vivo. Only surface expression of AnxA1 on monocytes correlated with dexamethasone-mediated suppression of cytokines. In ACS patients, a marked activation of AnxA1 was seen involving both gene expression and translocation of protein to cell surface probably reflecting a rapid glucocorticoid action modulating the acute inflammatory response in ACS. To conclude, surface expression of AnxA1 on monocytes may reflect the degree of glucocorticoid sensitivity. Speculatively, "normal" surface expression of AnxA1 indicates that anti-inflammatory capacity is impaired in SCAD patients.

  • 25.
    Bettoni, Serena
    et al.
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Shaughnessy, Jutamas
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, USA.
    Maziarz, Karolina
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Ermert, David
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Riesbeck, Kristian
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Blom, Anna
    Lund University - Department of Translational Medicine, Malmö, Sweden.
    Ram, Sanjay
    Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, USA.
    C4BP-IGM FUSION PROTEIN AS A NOVEL THERAPEUTIC APPROACH TO TREAT NEISSERIA GONORRHOEAE INFECTIONS2019In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 114, p. 470-470Article in journal (Other academic)
  • 26.
    Bjørkeng, Eva
    et al.
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway.
    Rasmussen, Gunlög
    Örebro University, School of Medical Sciences.
    Sundsfjord, Arnfinn
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Sjöberg, Lennart
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hegstad, Kristin
    Research Group for Host-Microbe Interactions, Department of Medical Biology, University of Tromsø, Tromsø, Norway; Department of Microbiology and Infection Control, Reference Centre for Detection of Antimicrobial Resistance, University Hospital of North-Norway, Tromsø, Norway.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases and Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Clustering of polyclonal VanB-type vancomycin-resistant Enterococcus faecium in a low-endemic area was associated with CC17-genogroup strains harbouring transferable vanB2-Tn5382 and pRUM-like repA containing plasmids with axe-txe plasmid addiction systems2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 4-5, p. 247-258Article in journal (Refereed)
    Abstract [en]

    VanB-type vancomycin-resistant Enterococcus faecium isolates (n = 17) from 15 patients at the Örebro University hospital in Sweden during a span of 18 months was characterized. All patients had underlying disorders and received broad-spectrum antimicrobial therapy. Pulsed-field gel electrophoresis (PFGE) grouped 14 isolates in three PFGE types and three isolates in unique PFGE patterns. All isolates had multi-locus sequence types [ST17 (n = 5); ST18 (n = 3); ST125 (n = 7); ST262 (n = 1); ST460 (n = 1)] belonging to the successful hospital-adapted clonal complex 17 (CC17), harboured CC17-associated virulence genes, were vanB2-positive and expressed diverse vancomycin minimum inhibitory concentration (MICs; 8 to > 256 mg/L). Isolate 1 had a unique PFGE type and a chromosomal transferable vanB2-Tn5382 element. Interestingly, the other five PFGE types had Tn5382 located on plasmids containing pRUM-like repA and a plasmid addiction system (axe-txe) shown by co-hybridization analysis of PFGE-separated S1-nuclease digested total DNA. The resistance plasmids were mainly of 120-kb and supported intraspecies vanB transfer. Two strains were isolated from patient 6 and we observed a possible transfer of the vanB2-resistance genes from PFGE type III ST460 to a more successful PFGE type I ST125. This latter PFGE type I ST125 became the predominant type afterwards. Our observations support the notion that vanB-type vancomycin-resistant Enterococcus faecium can persist in a low-endemic area through successful clones and plasmids with stability functions in hospital patients with known risk factors.

  • 27.
    Boiko, Iryna
    et al.
    WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Clinical Laboratory Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Krynytska, Inna
    Department of Functional and Laboratory Diagnostics, I. Horbachevsky Ternopil State Medical University, Ternopil, Ukraine.
    Bezkorovaina, Halyna
    Outpatient Department, Ternopil Regional Clinical Dermatovenerologic Dispensary, Ternopil, Ukraine.
    Frankenberg, Arkadii
    Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Onuchyna, Margarita
    Clinical Laboratory Department, Dnipropetrovsk Regional Clinical Dermatovenerologic Dispensary, Dnipro, Ukraine.
    Jacobsson, Susanne
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine.
    Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and treatment of gonorrhoea patients in Ternopil and Dnipropetrovsk regions of Ukraine, 2013-20182019In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 127, no 7, p. 503-509Article in journal (Refereed)
    Abstract [en]

    Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health concern globally. However, recent gonococcal AMR data from Eastern Europe are extremely limited and no AMR data for strains spreading in Ukraine have ever been internationally published. We investigated the AMR of N. gonorrhoeae isolates in two regions of Ukraine (Ternopil 2013-2018, Dnipropetrovsk 2013-2014), and, where information was available, the treatment administered to the corresponding gonorrhoea patients. Determination of minimum inhibitory concentration (MIC) of eight antimicrobials was performed using Etest and resistance breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Overall, 9.3% of the examined 150 isolates were resistant to ciprofloxacin, 6.0% to tetracycline, 2.0% to azithromycin, and 0.7% to benzylpenicillin. No isolates were resistant to ceftriaxone, cefixime, spectinomycin, or gentamicin. However, one (0.7%) isolate showed a MIC value of 0.125 mg/L for both ceftriaxone and cefixime, i.e., bordering resistance. Eighty-eight (67.2%) of 131 patients were administered dual therapy (ceftriaxone 1 g plus doxycycline/clarithromycin/azithromycin/ofloxacin) and 22 (16.8%) ceftriaxone 1 g monotherapy. Worryingly, 21 (16.0%) patients received monotherapy with clarithromycin/doxycycline/azithromycin/ofloxacin/benzylpenicillin. In conclusion, the antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipropetrovsk, Ukraine during 2013-2018 was high. Low levels of resistance to ciprofloxacin, tetracycline, azithromycin, and benzylpenicillin were found, but no resistance to the internationally recommended ceftriaxone, cefixime, or spectinomycin. Ceftriaxone 1 g should remain as empiric first-line treatment, in dual therapy with azithromycin or doxycycline or in monotherapy. Continued and expanded gonococcal AMR surveillance in Ukraine is essential to monitor the susceptibility to particularly extended-spectrum cephalosporins, azithromycin and doxycycline.

  • 28.
    Bozorg, Soran Rabin
    et al.
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm Sweden.
    Söderling, Jonas
    Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Sweden.
    Everhiv, Åsa H.
    Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Sweden; Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Lebwohl, Benjamin
    Celiac Disease Center, Department of Medicine, Columbia University Medical Centre, Columbia University, New York, USA.
    Green, Peter H. R.
    Celiac Disease Center, Department of Medicine, Columbia University Medical Centre, Columbia University, New York, USA.
    Neovius, Martin
    Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm Sweden; Celiac Disease Center, Department of Medicine, Columbia University Medical Centre, Columbia University, New York, USA; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
    Mårild, Karl
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; Department of Pediatric Gastroenterology, Queen Silvia Children’s Hospital, Gothenburg, Sweden.
    Work loss before and after diagnosis in patients with celiac disease2021In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 51, no Suppl. 1, p. 286-286Article in journal (Other academic)
    Abstract [en]

    Celiac disease (CD) is an immune‐mediated disease triggered by gluten intake and affects around 1% of the population worldwide. Although patients with CD have an increased use of healthcare, data on work disability remains scarce. To estimate work loss in patients with CD before and after diagnosis. We identified 16,005 working‐age patients with prevalent CD, and 4,936 incident working‐age patients diagnosed in 2008‐2015 through biopsy reports from Sweden’s 28 pathology departments. CD was defined by presence of villus atrophy (Marsh 3) on biopsy (gold standard). Each patient was compared to up to 5 matched general‐population comparators. Using nationwide social insurance registers, we retrieved prospectively‐recorded data on compensation for sick leave and disability. In 2015, patients with prevalent CD had a mean of 42.5 (95%CI: 40.9‐44.1) lost work days as compared with 28.6 (27.9‐29.2) in the general‐population comparators, corresponding to a relative difference of 49%. Among incident patients, the annual mean difference between patients and comparators was 8.0 (5.4‐10.6) lost work days 5 years before CD diagnosis, which grew to 13.7 (9.1‐18.3) days 5 years after diagnosis. In addition to the continuously increasing mean difference in lost work days over time, there was also a transient increase in work loss in patients with CD during the year of diagnosis (mean difference: 15.6 days, 95%CI: 13.1‐18.0). Patients with CD miss more work days than comparators before their diagnosis, and this loss increases and persists after diagnosis despite presumed installation of treatment with gluten‐free diet. 

  • 29.
    Braman Eriksson, Annika
    et al.
    Vårdcentralen Vansbro, Vansbro.
    Annsberg, Martin
    Vårdcentralen Sälen, Sälen.
    Hårdstedt, Maria
    Kardiologiska kliniken, Falu lasarett, Falun; Centrum för klinisk forskning (CKF) Dalarna/Uppsala universitet, Falun.
    Simningsorsakat lungödem vid svenska förhållanden otillräckligt studerat: erfarenheter från Vansbrosimningen 2016: [Swimming-induced pulmonary edema in Swedish conditions has been insufficiently studied]2017In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 114, no 25-26, article id ELXDArticle in journal (Other academic)
    Abstract [sv]

    Simningsorsakat lungödem (SIPE) är ett tillstånd med andnöd, hosta, skummande sputum och nedsatt fysisk ork vid simning i öppet vatten.

    Tidigare helt friska personer kan drabbas.

    Riskfaktorer som diskuteras är låg vattentemperatur, trång våtdräkt, brister i uppvärmning, övervätskning, hypertoni och tidigare simningsorsakat lungödem.

    Vid Vansbrosimningen 2016 sökte 69 personer (0,5 procent av simmarna) för andningsbesvär, flertalet med misstänkt simningsorsakat lungödem. Kvinnor var överrepresenterade.

    Prehospital behandling med CPAP gav god effekt. 

    Validerade råd till tävlingsarrangörer, simmare och sjukvård behöver utarbetas för att minska risken för simningsorsakat lungödem.

  • 30.
    Brehony, Carina
    et al.
    Dept Zool, Univ Oxford, Oxford, England..
    Trotter, Caroline L.
    Dept Vet Med, Univ Cambridge, Cambridge, England.
    Ramsay, Mary E.
    Publ Hlth England, London, England.
    Chandra, Manosree
    Publ Hlth England, London, England.
    Jolley, Keith A.
    Dept Zool, Univ Oxford, Oxford, England.
    van der Ende, Arie
    Dept Med Microbiol, Netherlands Reference Lab Bacterial Meningitis, Acad Med Ctr, Univ Amsterdam, Amsterdam, Netherlands.
    Carion, Francoise
    Meningococcal Reference Lab, Sci Inst Publ Hlth, Brussels, Belgium.
    Berthelsen, Lene
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hoffmann, Steen
    Neisseria & Streptococcus Reference Lab, Statens Serum Inst, Copenhagen, Denmark.
    Hardardottir, Hjordis
    Dept Microbiol, Landspitali Univ Hosp, Reykjavik, Iceland.
    Vazquez, Julio A.
    Meningococcal Reference Lab, Madrid, Spain.
    Murphy, Karen
    Irish Meningococcal & Meningitis Reference Lab, Dublin, Ireland.
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Canica, Manuela
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Ferreira, Eugenia
    Dept Infect Dis, Lab Antimicrobial Resistance, Natl Inst Hlth Dr Ricardo Jorge, Lisbon, Portugal.
    Diggle, Mathew
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Edwards, Giles F.
    Scottish Haemophilus Legionella Meningococcus & P, Glasgow, UK.
    Taha, Muhamed-Kheir
    Inst Pasteur, Natl Reference Ctr Meningococci, Institut Pasteur, Paris, France.
    Stefanelli, Paola
    Dept Infect Parasit & Immune Mediated Dis, Ist Super Sanita, Rome, Italy.
    Kriz, Paula
    Natl Reference Lab Meningococcal Infect, Natl Inst Publ Hlth, Prague, Czech Republic.
    Gray, Steve J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Fox, Andrew J.
    Meningococcal Reference Unit, Manchester Royal Infirm, Manchester, England.
    Jacobsson, Susanne
    Örebro University Hospital. National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Claus, Heike
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Vogel, Ulrich
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Tzanakaki, Georgina
    Natl Meningococcal Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Heuberger, Sigrid
    Natl Reference Ctr Meningococci, Inst Med Microbiol & Hyg, Graz, Austria.
    Caugant, Dominique A.
    Dept Bacteriol & Immunol, Norwegian Inst Publ Hlth, Oslo, Norway.
    Frosch, Matthias
    Inst Hyg & Mikrobiol, Wurzburg, Germany.
    Maiden, Martin C. J.
    Dept Zool, Univ Oxford, Oxford, England.
    Implications of Differential Age Distribution of Disease-Associated Meningococcal Lineages for Vaccine Development2014In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 21, no 6, p. 847-853Article in journal (Refereed)
    Abstract [en]

    New vaccines targeting meningococci expressing serogroup B polysaccharide have been developed, with some being licensed in Europe. Coverage depends on the distribution of disease-associated genotypes, which may vary by age. It is well established that a small number of hyperinvasive lineages account for most disease, and these lineages are associated with particular antigens, including vaccine candidates. A collection of 4,048 representative meningococcal disease isolates from 18 European countries, collected over a 3-year period, were characterized by multilocus sequence typing (MLST). Age data were available for 3,147 isolates. The proportions of hyperinvasive lineages, identified as particular clonal complexes (ccs) by MLST, differed among age groups. Subjects <1 year of age experienced lower risk of sequence type 11 (ST-11) cc, ST-32 cc, and ST-269 cc disease and higher risk of disease due to unassigned STs, 1- to 4-year-olds experienced lower risk of ST-11 cc and ST-32 cc disease, 5- to 14-year-olds were less likely to experience ST-11 cc and ST-269 cc disease, and >= 25-year-olds were more likely to experience disease due to less common ccs and unassigned STs. Younger and older subjects were vulnerable to a more diverse set of genotypes, indicating the more clonal nature of genotypes affecting adolescents and young adults. Knowledge of temporal and spatial diversity and the dynamics of meningococcal populations is essential for disease control by vaccines, as coverage is lineage specific. The nonrandom age distribution of hyperinvasive lineages has consequences for the design and implementation of vaccines, as different variants, or perhaps targets, may be required for different age groups.

  • 31.
    Brew, Bronwyn K.
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Gong, Tong
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet; Sweden Pediatric Allergy and Pulmonology Unit,t Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    The familial aggregation of atopic diseases and depression or anxiety in children2018In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 48, no 6, p. 703-711Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Children with asthma and atopic diseases have an increased risk of depression or anxiety. Each of these diseases have strong genetic and environmental components, therefore it seems likely that there is a shared liability rather than causative risk.

    OBJECTIVE: To investigate the existence and nature of familial aggregation for the comorbidity of atopic diseases and depression or anxiety.

    METHODS: Participants came from the Childhood and Adolescent Twin Study in Sweden (CATSS), n= 14197. Current and ever asthma, eczema, hayfever and food-allergy were reported by parents. Internalizing disorders were identified using validated questionnaires. Familial co-aggregation analysis compared monozygotic MZ twins and same-sex dizygotic DZ twins for atopic disease in one twin with internalizing disorder in the other to test for genetic liability. Several familial liability candidates were also tested including parental education, recent maternal psychological stress, childhood family trauma and parental country of birth.

    RESULTS: Familial co-aggregation analysis found that if one twin had at least one current atopic disease the partner twin was at risk of having an internalizing disorder regardless of their own atopic status (Adjusted OR 1.22 (95% CI 1.08, 1.37). Similar results were found for each atopic disease ever and current. MZ associations were not higher than DZ associations suggesting that the liability is not genetic in nature. Including other familial candidates to the models made little difference to effect estimates.

    CONCLUSIONS AND CLINICAL RELEVANCE: Atopic diseases and depression or anxiety tend to occur together in families, therefore when treating for one disease the physician should consider comorbidity in both the individual and the individual's siblings. We did not find evidence to support a genetic explanation for comorbidity and further exploration is needed to disentangle the environmental and epigenetic reasons for familial aggregation.

  • 32.
    Broeker, Michael
    et al.
    Novartis Vaccines & Diagnost GmbH, Marburg, Germany.
    Bukovski, Suzana
    Univ Hosp Infect Dis Dr Fran Mihaljevic, Zagreb, Croatia.
    Culic, Davor
    Haemophilus & Meningococcus Reference Lab, Ctr Microbiol, Inst Publ Hlth, Srbija, Serbia.
    Jacobsson, Susanne
    Örebro University Hospital.
    Koliou, Maria
    Unit Surveillance & Control Communicable Dis, Minist Hlth, Nikosia, Cyprus.
    Kuusi, Markku
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Simoes, Maria Joao
    Inst Nacl Saude Dr Ricardo Jorge, Lisbon, Portugal.
    Skoczynska, Anna
    Natl Reference Ctr Bacterial Meningitis, Natl Med Inst, Warsaw, Poland.
    Toropainen, Maija
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Taha, Muhamed-Keir
    Invas Bacterial Infect Unit, Inst Pasteur, Paris, France.
    Tzanakaki, Georgina
    Natl Meningitis Reference Lab, Natl Sch Publ Hlth, Athens, Greece.
    Meningococcal serogroup Y emergence in Europe High importance in some European regions in 20122014In: Human Vaccines & Immunotherapeutics, ISSN 2164-5515, E-ISSN 2164-554X, Vol. 10, no 6, p. 1725-1728Article in journal (Refereed)
    Abstract [en]

    Neisseria meningitidis is differentiated into 12 distinct serogroups, of which A, B, C, W, X, and Y are medically most important and represent an important health problem in different parts of the world. The epidemiology of N. meningitidis is unpredictable over time and across geographic regions. Recent epidemiological surveillance has indicated an increase of serogroup Y invasive meningococcal disease in some parts of Europe as shown in the epidemiological data for 2010 and 2011 from various European countries previously published in this journal. 1,2 Here, data from 33 European countries is reported indicating that the emergence of serogroup Y continued in 2012 in various regions of Europe, especially in Scandinavia, while in Eastern and South-Eastern Europe the importance of serogroup Y remained low.

  • 33.
    Butwicka, Agnieszka
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden;.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden .
    Frisén, Louise
    Child and Adolescent Psychiatry Research Center, Stockholm, Sweden; Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
    Larsson, Henrik
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, United States.
    Celiac disease is associated with childhood psychiatric disorders: A Population-Based Study2017In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 184, p. 87-93.e1, article id S0022-3476(17)30153-1Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To determine the risk of future childhood psychiatric disorders in celiac disease, assess the association between previous psychiatric disorders and celiac disease in children, and investigate the risk of childhood psychiatric disorders in siblings of celiac disease probands.

    STUDY DESIGN: This was a nationwide registry-based matched cohort study in Sweden with 10 903 children (aged <18 years) with celiac disease and 12 710 of their siblings. We assessed the risk of childhood psychiatric disorders (any psychiatric disorder, psychotic disorder, mood disorder, anxiety disorder, eating disorder, psychoactive substance misuse, behavioral disorder, attention-deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and intellectual disability). HRs of future psychiatric disorders in children with celiac disease and their siblings was estimated by Cox regression. The association between previous diagnosis of a psychiatric disorder and current celiac disease was assessed using logistic regression.

    RESULTS: Compared with the general population, children with celiac disease had a 1.4-fold greater risk of future psychiatric disorders. Childhood celiac disease was identified as a risk factor for mood disorders, anxiety disorders, eating disorders, behavioral disorders, ADHD, ASD, and intellectual disability. In addition, a previous diagnosis of a mood, eating, or behavioral disorder was more common before the diagnosis of celiac disease. In contrast, siblings of celiac disease probands were at no increased risk of any of the investigated psychiatric disorders.

    CONCLUSIONS: Children with celiac disease are at increased risk for most psychiatric disorders, apparently owing to the biological and/or psychological effects of celiac disease.

  • 34. Chiu Götlind, Y. Y.
    et al.
    Raghavan, S.
    Bland, P. W.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    CD4+FoxP3+ regulatory T cellsare functionally active in the Gαi2−/− mouse, but do not prevent thedevelopment of colitis2010Conference paper (Other academic)
  • 35.
    Consiglio, Camila
    et al.
    Lund University, Department of Laboratory Medicine, Lund, Sweden; Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden .
    Tadepally, Lakshmikanth
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Sardh, Fabian
    Karolinska Institutet, Department of Medicine Solna, Solna, Sweden; Uppsala University, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden.
    Forlin, Rikard
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Wang, Jun
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Tan, Ziyang
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Barcenilla, Hugo
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Rodriguez, Lucie
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Sugrue, Jamie
    Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France.
    Noori, Peri
    Karolinska Institutet, Department of Medicine Solna, Solna, Sweden.
    Páez, Laura P.
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Gonzalez, Laura
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Mugabo, Constantin H.
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Johnsson, Annette
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Department of Medicine Solna, Solna, Sweden.
    Pou, Christian
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Chen, Yang
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Mikes, Jaromir
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    James, Anna
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden.
    Dahlqvist, Per
    Umeå University, Department of Public Health and Clinical Medicine, Umeå, Sweden.
    Wahlberg, Jeanette
    Örebro University, School of Medical Sciences.
    Hagelin, Anders
    Karolinska University Hospital, ANOVA, Stockholm, Sweden; Karolinska Institutet, Department of Medicine Huddinge, Stockholm, Sweden.
    Holmberg, Mats
    Karolinska University Hospital, ANOVA, Stockholm, Sweden; Karolinska Institutet, Department of Medicine Huddinge, Stockholm, Sweden.
    Degerblad, Marie
    Karolinska Institutet, Endocrinology and Diabetes Unit, Department of Molecular Medicine and Surgery, Solna, Sweden.
    Isaksson, Magnus
    Uppsala University, Department of Medical Sciences, Uppsala, Sweden.
    Duffy, Darragh
    Institut Pasteur, Université Paris Cité, Translational Immunology Unit, Paris, France.
    Kämpe, Olle
    Karolinska Institutet, Department of Medicine Solna, Solna, Sweden; Karolinska University Hospital, Center of Molecular Medicine, and Department of Endocrinology, Metabolism and Diabetes, Stockholm, Sweden.
    Landegren, Nils
    Karolinska Institutet, Department of Medicine Solna, Solna, Sweden; Uppsala University, Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala, Sweden.
    Brodin, Petter
    Karolinska Institutet, Unit for Clinical Pediatrics, Dept. of Women’s and Children’s Health, Solna, Sweden; Imperial College London, Department of Immunology and Inflammation, London, UK.
    Immune system adaptation during gender-affirming testosterone treatment2023In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 159, p. 29-30Article in journal (Other academic)
    Abstract [en]

    Biological sex impacts human immune responses, modulating susceptibility and severity to immune-related diseases. Female generally mount more robust immune responses than males, resulting in lower infection severity and greater autoimmunity incidence. Here, we addressed the contribution of testosterone to human immune function by analyzing a cohort of subjects undergoing gender-affirming testosterone treatment. We performed systems-level immunomonitoring through mass cytometry, scRNA and scA-TAC-Sequencing, and proteome profiling of blood samples at baseline and following 3 and 12 months of treatment. Testosterone treatment was associated with a low-grade inflammatory profile, evidenced by upregulation of proinflammatory plasma proteome (e.g., EN-RAGE, OSM, TNF), and induction of an inflammatory transcriptional program associated with NFkB signaling, and TNF signaling. Following testosterone treatment, higher NFkB activity was revealed in CD4 T, CD8 T, and NK cells in scATACseq analyses. Further, testosterone increased monocytic inflammatory responses upon bacterial stimulation in vitro. Although testosterone was associated with this inflammatory profile, it also exerted negative effects on antiviral immunity. Firstly, the percentage of plasmacytoid dendritic cells (pDC) decreased over transition, with pDC also displaying phenotypic changes associated with lower IFN responses. Secondly, bulk transcriptomics analyses show an overall reduction of IFNa responses. Thirdly, testosterone treatment led to reduced IFNa production upon PBMCs stimulation with a viral agonist. Our results show that testosterone has broad effects on the human immune system, and significantly modulates important players in antiviral immunity and inflammatory response. Identifying pathways involved in immune sexual dimorphism will help define novel targets for effective prevention and treatment of immune-mediated diseases.

  • 36.
    Davey, Dvora Joseph
    et al.
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique; Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles CA, USA.
    Nhavoto, José Antonio
    Örebro University, Örebro University School of Business. Department of Mathematics and Informatics, Eduardo Mondlane University, Maputo, Mozambique.
    Augusto, Orvalho
    Department of Community Health, Eduardo Mondlane University, Maputo, Mozambique.
    Ponce, Walter
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique.
    Traca, Daila
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique.
    Nguimfack, Alexandre
    Mozambique HIV care and treatment - Ark, Maputo, Mozambique.
    de Sousa, Cesar Palha
    Department of Community Health, Eduardo Mondlane University, Maputo, Mozambique.
    SMSaude: Evaluating Mobile Phone Text Reminders to Improve Retention in HIV Care for Patients on Antiretroviral Therapy in Mozambique2016In: Journal of Acquired Immune Deficiency Syndromes, ISSN 1525-4135, E-ISSN 1944-7884, Vol. 73, no 2, p. E23-E30Article in journal (Refereed)
    Abstract [en]

    Objective: We evaluated whether regular mobile phone text reminders improved patients' retention in antiretroviral therapy (ART) care in Mozambique.

    Design: SMSaude was a randomized control trial of HIV-infected patients on ART who received regular text message reminder vs. standard of care at 3 public health facilities in Maputo Province, Mozambique. The primary outcome was retention in HIV care. Between November 2011 and March 2012, 830 eligible HIV-infected patients on ART were randomized 1: 1 to the text reminder intervention or standard of care.

    Methods: We used Kaplan-Meier estimators and log-rank tests to compare proportions of patients who received SMS reminders who were retained in HIV care compared to the control group who received standard of care. Post hoc analyses were performed using Cox proportional hazards models stratified by urban/rural facility and when initiated ART (<= 3 months vs. >3 months). Hazard ratios and confidence intervals (CIs) are reported. Analysis was with intention to treat.

    Results: Patients who received text messages had lower attrition from HIV care at 12 months, though the difference was nonsignificant (RR: 0.68, 95% CI: 0.41 to 1.13). Among urban patients, text messages improved retention in HIV care (RR: 0.54, 95% CI: 0.31 to 0.95). Intervention patients newly initiated on ART (<3 months) had lower attrition than control patients (HR: 0.54; 95% CI: 0.23 to 0.91), especially urban newly initiated patients (HR: 0.20, 95% CI: 0.06 to 0.64). Text messages had no effect on retention among rural patients.

    Conclusions: Text messages did not improve retention in HIV care for all patients on ART but improved retention in care of urban patients and those who recently started ART and received text reminders compared with standard of care.

  • 37.
    Davidsson, Sabina
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden .
    Mölling, Paula
    Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Rider, Jennifer R.
    Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats G.
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Pathology, Örebro University Hospital, Örebro, Sweden.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Elgh, Fredrik
    Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden; A Member of the Transdisciplinary Prostate Cancer Partnership (TopCaP), Örebro, Sweden.
    Erratum to: Frequency and typing of Propionibacterium acnes in prostate tissue obtained from men with and without prostate cancer2016In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 11, article id 36Article in journal (Refereed)
  • 38.
    Demirel, Isak
    et al.
    Örebro University, School of Medical Sciences.
    Persson, Alexander
    Örebro University, School of Medical Sciences.
    Brauner, Annelie
    Department of Microbiology, Tumor and Cell Biology, Division of Clinical Microbiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Kruse, Robert
    Örebro University, School of Medical Sciences. Department of Clinical Research Laboratory, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Persson, Katarina
    Örebro University, School of Medical Sciences.
    Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells2018In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 8, article id 81Article in journal (Refereed)
    Abstract [en]

    The NLRP3 inflammasome and IL-1 beta release have recently been suggested to be important for the progression of urinary tract infection (UTI). However, much is still unknown regarding the interaction of UPEC and the NLRP3 inflammasome. The purpose of this study was to elucidate what virulence factors uropathogenic Escherichia coil (UPEC) use to modulate NLRP3 inflammasome activation and subsequent IL-1 beta release and the role of NLRP3 for UPEC colonization of bladder epithelial cells. The bladder epithelial cell line 5637, CRISPR/Cas9 generated NLRP3, caspase-1 and mesotrypsin deficient cell lines and transformed primary bladder epithelial cells (HBLAK) were stimulated with UPEC isolates and the non-pathogenic MG1655 strain. We found that the UPEC strain CFT073, but not MG1655, induced an increased caspase-1 activity and IL-1 beta release from bladder epithelial cells. The increase was shown to be mediated by et-hemolysin activation of the NLRP3 inflammasome in an NE-kappa B-independent manner. The effect of-hemolysin on IL-1 beta release was biphasic, initially suppressive, later inductive. Furthermore, the phase-locked type-1-fimbrial ON variant of CFT073 inhibited caspase-1 activation and IL-1 beta release. In addition, the ability of CFT073 to adhere to and invade NLRP3 deficient cells was significantly reduced compare to wild-type cells. The reduced colonization of NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and alpha-hemolysin can modulate the activity of the NLRP3 inflammasome.

  • 39.
    Drobin, Kimi
    et al.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Assadi, Ghazaleh
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Hong, Mun-Gwan
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Andersson, Eni
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Fredolini, Claudia
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Forsström, Björn
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    Reznichenko, Anna
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Akhter, Tahmina
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
    Ek, Weronica E.
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Bonfiglio, Ferdinando
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; Department of Gastrointestinal and Liver Diseases, Biodonostia Health Research Institute, San Sebastián, Spain.
    Hansen, Mark Berner
    AstraZeneca R&D Mölndal, Innovative and Global Medicines, Mölndal, Sweden; Digestive Disease Center, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
    Sandberg, Kristian
    Science for Life Laboratory, Drug Discovery & Development Platform & Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Greco, Dario
    Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Schwenk, Jochen M.
    Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Stockholm, Sweden.
    D'Amato, Mauro
    Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden; BioDonostia Health Research Institute, San Sebastian, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed)
    Abstract [en]

    Background: Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential.

    Methods: Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohn's disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping.

    Results: By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity.

    Conclusions: Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

  • 40.
    Dvorak, C.M.T.
    et al.
    University of Minnesota, Minnesota, USA.
    Hårdstedt, Maria
    University of Minnesota, Minnesota, USA.
    Xie, H.
    University of Minnesota, Minnesota, USA.
    Wang, M.
    University of Minnesota, Minnesota, USA.
    Papas, K.K.
    University of Minnesota, Minnesota, USA.
    Hering, Bernhard J.
    University of Minnesota, Minnesota, USA.
    Murtaugh, M.P.
    University of Minnesota, Minnesota, USA.
    Fahrenkrug, S.C.
    University of Minnesota, Minnesota, USA.
    Transcriptional profiling of stress response in cultured porcine islets2007In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 357, no 1, p. 118-125Article in journal (Refereed)
    Abstract [en]

    Cell-based diabetes therapy may be achieved through xenotransplantation of adult porcine islets, but tissue quality and immunoreactivity barriers need to be overcome. Early identification and exclusion of irreversibly stressed and dying islets may improve transplant outcomes. We used oligonucleotide microarray and quantitative RT-PCR to identify molecular markers of physiological and immunological stress in porcine islets cultured under stress conditions of elevated glucose (16.7 mM), inflammatory cytokine addition (IL-1beta, TNF-alpha, and IFN-gamma), or both, for 48 h. Hyperglycemic conditions were associated with increased thioredoxin interacting protein and metabolic process mRNAs, as observed in rodent and primate species. Cytokine treatment increased expression of JAK-STAT pathway components, oxidative stress (transglutaminase 2), and beta cell dysfunction genes. Transglutaminase 2 induction is unique to porcine islets. Biomarkers involved in hyperglycemia and islet inflammation may serve as novel targets for improving and monitoring isolated porcine islet function and viability.

  • 41.
    Edström, Måns
    Örebro University, School of Medical Sciences. Örebro University Hospital. Linköpings universitet, Avdelningen för inflammationsmedicin.
    Regulation of immunity in Multiple Sclerosis: CD4+ T cells and the influence of natalizumab2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) and the most common neurological cause of disability in young adults. In most cases, the disease course is characterised by the cycling of relapses and remissions, so called relapsing-remitting MS (RR-MS). Although extensively studied, the underlying mechanisms are not fully elucidated, yet CD4+ T cells have been shown to be of importance in disease pathology. A range of treatments are available; the most effective to date being natalizumab, a monoclonal antibody directed against the adhesion molecule VLA-4 on the lymphocyte surface, thereby preventing entry into the CNS.

    The aim of this thesis was to assess the nature of lymphocyte populations in MS. This was achieved by studying CD4+ T helper cells (TH) and regulatory T cells (TREG) in peripheral blood. In addition, the influence of natalizumab was also investigated, both regarding the effect of the drug on the composition of the peripheral lymphocyte compartment as well as its effects on CD4+ T cells in vitro.

    We showed an imbalance in the mRNA expression of CD4+ T helper cell lineage specific transcription factors in peripheral blood. While TH1 and TH17 associated TBX21 and RORC expression was comparable in MS and healthy individuals, the TH2 and TREG associated GATA3 and FOXP3 expression was decreased in RR-MS. Given the reciprocally inhibitory nature of TH subsets, this might imply not only diminished function of TH2 and TREG cells but also a permissive state of harmful TH1 and TH17 cells. The size of the peripheral TREG population was unaltered in RR-MS. When analysed in detail, activated and resting TREG were distinguished, showing clear differences in FOXP3 and CD39 expression. Furthermore, when investigating these subpopulations functionally, the ability of activated TREG to suppress proliferation of responder T cells was found to be decreased in RR-MS patients compared to controls. To further investigate this defect, the global gene expression of TREG was compared between patients and controls. Gene set enrichment analysis revealed an enrichment (over-expression) of chemokine receptor signalling genes in RR-MS TREG, possibly suggesting a role for  chemokines in TREG function.

    A sizable effect of natalizumab treatment was seen in the composition of peripheral lymphocyte populations after one year of treatment. While the number of lymphocytes increased over all, the largest increase was seen in the NK and B cell compartments. Furthermore, T cells from patients with MS displayed decreased responsiveness towards antigens and mitogens in vitro. Natalizumab treatment was able to normalise the responsiveness in blood, an effect not solely dependent on the increased number of cells.

    The importance of CD4+ T cells in human disease, including MS, was shown by a systems biology approach; using GWAS data, genes associated with CD4+ T cell differentiation were enriched for many, not only immunerelated, diseases. Furthermore, global CD4+ T cell gene expression (by microarray) could discriminate between patients and controls. Lastly, using in vitro treated CD4+ T cells, we could show that natalizumab perturbated gene expression differently in patients responding to the drug compared to those not responding.

    In conclusion, our results demonstrate an imbalance of peripheral CD4+ T cells in MS, along with a functional deficiency in the case of TREG. Taken together, these aberrations might result in differentiation and activation of harmful TH1 and TH17 cells, resulting in CNS tissue damage. The importance of CD4+ T cells was further demonstrated by the finding that genes associated with CD4+ T cell differentiation constitute a pleiotropic module common to a number of diseases. Investigation of natalizumab revealed drastic changes in the peripheral lymphocyte compartment caused by treatment. It also appears as treatment might influence the responsiveness of peripheral T cells to antigens. In addition, by using CD4+ T cell transcriptomics after in vitro drug exposure, prediction of treatment outcome may be possible.

  • 42.
    El Marghani, Ahmed
    Örebro University, Department of Natural Sciences.
    Cell signaling in inflammatory diseases and development of antiinflammatory drugs2008Licentiate thesis, monograph (Other academic)
    Download (pdf)
    omslag
  • 43.
    Elgbratt, Kristina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Jansson, Andreas
    Systems Biology Research Centre, University of Skövde, Skövde, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    A quantitative study of the mechanisms behind thymic atrophy in G alpha i2-deficient mice during colitis development2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 5, article id e36726Article in journal (Refereed)
    Abstract [en]

    Mice deficient for the G protein subunit G alpha i2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The G alpha i2(-/-) mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the G alpha i2(-/-) mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai2(-/-) mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the G alpha i2(-/-) SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. G alpha i2(-/-) mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis.

  • 44. Eliasson, Henrik
    et al.
    Olcén, Per
    Sjöstedt, Anders
    Jurstrand, Margareta
    Bäck, Erik
    Örebro University, School of Health and Medical Sciences.
    Andersson, Sören
    Örebro University, School of Health and Medical Sciences.
    Kinetics of the immune response associated with tularemia: comparison of an enzyme-linked immunosorbent assay, a tube agglutination test, and a novel whole-blood lymphocyte stimulation test2008In: Clinical and Vaccine Immunology, ISSN 1556-6811, E-ISSN 1556-679X, Vol. 15, no 8, p. 1238-1243Article in journal (Refereed)
    Abstract [en]

    We have developed and evaluated a novel and simplified whole-blood lymphocyte stimulation assay that focuses on the measurement of gamma interferon after 24 h of stimulation with whole-cell tularemia antigen and a tularemia enzyme-linked immunosorbent assay (ELISA) based on highly purified lipopolysaccharide antigen. Comparison of the kinetics of the two assays and those of the traditional tube agglutination test shows that the cellular immune response can be detected earlier by the lymphocyte stimulation assay. This test already shows a high proportion of positive results during the first week after the onset of the disease, may be applicable in everyday laboratory practice, and has the potential of changing routine diagnostics for tularemia. The new ELISA has a high sensitivity and becomes positive to a high degree during the second week of disease. 

  • 45.
    El-Rami, Fadi E.
    et al.
    Pharmaceutical Sciences, Oregon State University, United States of America.
    Zielke, Ryszard A.
    College of Pharmacy, Oregon State University, United States of America.
    Wi, Teodora
    World Health Organization, Geneva, Switzerland.
    Sikora, Aleksandra E.
    Department of Pharmaceutical Sciences, Oregon State University, United States of America; Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton OR, United States.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization, Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Quantitative proteomics of the 2016 WHO Neisseria gonorrhoeae reference strains surveys vaccine candidates and antimicrobial resistance determinants2019In: Molecular & Cellular Proteomics, ISSN 1535-9476, E-ISSN 1535-9484, Vol. 18, no 1, p. 127-150Article in journal (Refereed)
    Abstract [en]

    The sexually transmitted disease gonorrhea (causative agent: Neisseria gonorrhoeae) remains an urgent public health threat globally due to its reproductive health repercussions, high incidence, widespread antimicrobial resistance (AMR), and absence of a vaccine. To mine gonorrhea antigens and enhance our understanding of gonococcal AMR at the proteome level, we performed the first large-scale proteomic profiling of a diverse panel (n=15) of gonococcal strains, including the 2016 World Health Organization (WHO) reference strains. These strains show all existing AMR profiles - established through phenotypic characterization and reference genome publication - and are intended for quality assurance in laboratory investigations. Herein, these isolates were subjected to subcellular fractionation and labeling with tandem mass tags coupled to mass spectrometry and multi-combinatorial bioinformatics. Our analyses detected 904 and 723 common proteins in cell envelope and cytoplasmic subproteomes, respectively. We identified nine novel gonorrhea vaccine candidates. Expression and conservation of new and previously selected antigens were investigated. In addition, established gonococcal AMR determinants were evaluated for the first time using quantitative proteomics. Six new proteins, WHO_F_00238, WHO_F_00635c, WHO_F_00745, WHO_F_01139, WHO_F_01144c, and WHO_F_01126, were differentially expressed in all strains, suggesting that they represent global proteomic AMR markers, indicate a predisposition toward developing or compensating gonococcal AMR, and/or act as new antimicrobial targets. Finally, phenotypic clustering based on the isolates' defined antibiograms and common differentially expressed proteins yielded seven matching clusters between established and proteome-derived AMR signatures. Together, our investigations provide a reference proteomics databank for gonococcal vaccine and AMR research endeavors, which enables microbiological, clinical, or epidemiological projects and enhances the utility of the WHO reference strains.

  • 46.
    Esbjörnsson, Joakim
    et al.
    Department of Laboratory Medicine, Lund University, Malmö, Sweden; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
    Månsson, Fredrik
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Kvist, Anders
    Department of Clinical Sciences Lund, Lund University, Malmö, Sweden.
    da Silva, Zacarias J.
    National Public Health Laboratory, Bissau, Guinea-Bissau.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Fenyö, Eva Maria
    Department of Laboratory Medicine, Lund University, Malmö, Sweden.
    Isberg, Per-Erik
    Department of Statistics, Lund University School of Economics and Management, Lund, Sweden.
    Biague, Antonio J.
    National Public Health Laboratory, Bissau, Guinea-Bissau.
    Lindman, Jacob
    Department of Clinical Sciences Lund, Lund University, Malmö, Sweden.
    Palm, Angelica A.
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Rowland-Jones, Sarah L.
    Nuffield Department of Medicine, University of Oxford, Oxford, UK.
    Jansson, Marianne
    Department of Laboratory Medicine, Lund University, Malmö, Sweden.
    Medstrand, Patrik
    Department of Translational Medicine, Lund University, Malmö, Sweden.
    Norrgren, Hans
    Department of Clinical Sciences Lund, Lund University, Malmö, Sweden.
    Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study2019In: The Lancet HIV, ISSN 2405-4704, E-ISSN 2352-3018, Vol. 6, no 1, p. E25-E31Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: HIV type 2 (HIV-2) is considered more benign and has fewer pathogenic consequences than HIV type 1 (HIV-1) for most infected individuals. However, reliable estimates of time to AIDS and mortality among those with HIV-2 infection are absent. We therefore aimed to compare the time to AIDS and mortality, and the CD4 T-cell dynamics between those infected with HIV-1 and HIV-2.

    METHODS: We did a prospective open cohort study. We included all police officers with regular employment from police stations in both urban and rural areas of Guinea-Bissau since Feb 6, 1990. We continued to include participants until Sept 28, 2009, and follow-up of HIV-1-positive and HIV-2-positive individuals continued until Sept 28, 2013. We collected blood samples at enrolment and at scheduled annual follow-up visits at police stations. We analysed longitudinal data from individuals infected with HIV-1 and HIV-2 according to time to AIDS, time to death, and T-cell dynamics. Time of HIV infection was estimated as the mid-timepoint between last HIV-seronegative and first HIV-seropositive sample. Data from an additional 2984 HIV-uninfected individuals from the same population were analysed to assess the effect of natural mortality on HIV-related mortality.

    FINDINGS: 872 participants tested HIV positive during the 23-year study period: 408 were infected with HIV-1 (183 infected before and 225 infected after enrolment) and 464 were infected with HIV-2 (377 before and 87 after enrolment). The median time from HIV infection to development of AIDS was 6·2 years (95% CI 5·4-7·1) for HIV-1 infection and 14·3 years (10·7-18·0) for HIV-2 infection (p<0·0001). The median survival time after HIV infection was 8·2 years (95% CI 7·5-8·9) for HIV-1 infection and 15·6 years (12·0-19·2) for HIV-2 infection (p<0·0001). Individuals who were infected with HIV-1 or HIV-2 before enrolment showed similar results. Comparison with uninfected individuals indicated limited confounding contribution from natural mortality. Mean CD4 percentages were higher in individuals with HIV-2 than in those with HIV-1 during early infection (28·0% [SE 1·3] vs 22·3% [1·7]; p=0·00094) and declined at a slower rate (0·4% [0·2] vs 0·9% [0·2] per year; p=0·028). HIV-2-infected individuals developed clinical AIDS at higher mean CD4 percentages (18·2%, IQR 7·2-25·4) than HIV-1-infected individuals (8·2%, 3·0-13·8; p<0·0001).

    INTERPRETATION: Our results show that both HIV-1-infected and HIV-2-infected individuals have a high probability of developing and dying from AIDS without antiretroviral treatment.

  • 47.
    Fant, F.
    et al.
    Department of Anesthesiology and Intensive Care, University Hospital, Örebro, Sweden.
    Tina, Elisabet
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Clinical Research Centre.
    Sandblom, D.
    Department of Urology and the Health Academy, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    Department of Urology and the Health Academy, Örebro University Hospital, Örebro, Sweden.
    Magnuson, A.
    Clinical Epidemiology and Biostatistical Unit, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden.
    Axelsson, Kjell
    Department of Anesthesiology and Intensive Care, University Hospital, Örebro, Sweden.
    Gupta, Anil
    Department of Anesthesiology and Intensive Care, University Hospital, Örebro, Sweden.
    Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy2013In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 110, no 5, p. 747-757Article in journal (Refereed)
    Abstract [en]

    Background: Epidural anaesthesia and analgesia has been shown to suppress the neurohormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropubic prostatectomy.

    Methods: Twenty-six patients were randomized to Group P (systemic opioid-based analgesia) or Group E (thoracic epidural-based analgesia) perioperatively. Induction and maintenance of anaesthesia followed a standardized protocol. The following measurements were made perioperatively: plasma cortisol, glucose, insulin, C-reactive proteins, leucocyte count, plasma cytokines [interleukin (IL)-6, tumour necrosis factor (TNF)-alpha], and pokeweed mitogen-stimulated cytokines [interferon (IFN)-gamma, IL-2, IL-12p70, IL-10, IL-4, and IL-17]. Other parameters recorded were pain, morphine consumption, and perioperative complications.

    Results: Plasma concentration of cortisol and glucose were significantly higher in Group P compared with Group E at the end of surgery, the mean difference was 232 nmol litre(-1) [95% confidence interval (CI) 84-381] (P=0.004) and 1.6 mmol litre(-1) (95% CI 0.6-2.5) (P=0.003), respectively. No significant differences were seen in IL-6 and TNF-alpha at 24 h (P=0.953 and 0.368, respectively) and at 72 h (P=0.931 and 0.691, respectively). IL-17 was higher in Group P compared with Group E, both at 24 h (P=0.001) and 72 h (P=0.018) after operation. Pain intensity was significantly greater in Group P compared with Group E (P<0.05) up to 24 h.

    Conclusions: In this small prospective randomized study, thoracic epidural analgesia reduced the early postoperative stress response but not the acute inflammatory response after radical retrobupic prostatectomy, suggesting that other pathways are involved during the acute phase reaction.

  • 48.
    Fransén, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Hiyoshi, Ayako
    Örebro University, School of Medical Sciences.
    Hurtig Wennlöf, Anita
    Jönköping University, Jönköping.
    The C10X Polymorphism in the CARD8 Gene is Associated with the Levels of CCL20 and IL-6 Proteins in Healthy Young Men2023In: Circulation Research, ISSN 0009-7330, E-ISSN 1524-4571, Vol. 133, article id AP3010Article in journal (Other academic)
  • 49.
    Fransén, Karin
    et al.
    Örebro University, School of Medical Sciences.
    Pettersson, Carolina
    Clinical Research Laboratory, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hurtig-Wennlöf, Anita
    School of Health and Welfare, Jönköping University, Sweden.
    CRP levels are significantly associated with CRP genotype and estrogen use in The Lifestyle, Biomarker and Atherosclerosis (LBA) study2022In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 22, no 1, article id 170Article in journal (Refereed)
    Abstract [en]

    Background: The C‑reactive protein (CRP) is an important biomarker for atherosclerosis and single nucleotide poly‑morphisms (SNPs) in the CRP locus have been associated with altered CRP levels and associated with risk for cardio‑vascular disease. However, the association between genetic variations in the CRP gene, estrogen use and CRP levels orearly signs of atherosclerosis in young healthy individuals is not fully characterized. We aimed to evaluate the influ‑ence of five genetic variants on both plasma CRP levels and carotid intima‑media thickness (cIMT) values, includingaspects on estrogen containing contraceptive use in females.

    Methods: Genotyping was performed with TaqMan real time PCR and compared with high sensitivity CRP serumlevels in 780 Swedish young, self‑reported healthy individuals. Haplotypes of the SNPs were estimated with the PHASEv 2.1. The cIMT was measured by 12 MHz ultrasound. The contraceptive use was self‑reported.

    Results: Strong associations between CRP and genotype were observed for rs3091244, rs1800947, rs1130864, andrs1205 in women (all p < 0.001). In men, only rs1800947 was associated with CRP (p = 0.029). The independent effectof genotypes on CRP remained significant also after adjustment for established risk factors. Female carriers of the H1/ATGTG haplotype had higher CRP than non‑carriers. This was specifically pronounced in the estrogen‑using group(p < 0.001), and they had also higher cIMT (p = 0.002) than non‑carriers but with a small cIMT difference between thehaplotype groups (0.02 mm). In parallel, a significant correlation between CRP and cIMT in the estrogen using groupwas observed (r = 0.194; p = 0.026).

    Conclusions: Estrogen use, genotypes and haplotypes in the CRP locus are significantly associated with CRP levels.Based on an observed interaction effect between sex/estrogen use and the H1/ATGTG haplotype on CRP, and amarginally thicker cIMT in the estrogen using group, our data suggest that both genotypes and estrogen usage couldbe involved in arterial wall structural differences. The causality between CRP levels and cIMT remains unclear, and theobserved difference in cIMT is not clinically relevant in the present state. Future larger and longitudinal studies mayshed further light on the role of more long‑term estrogen use and early atherosclerosis.

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  • 50.
    Fritsch Fredin, Maria
    et al.
    Astra-Zeneca, Mölndal.
    Hultin, Leif
    Astra-Zeneca, Mölndal.
    Hyberg, Gina
    Astra-Zeneca, Mölndal.
    Rehnström, Erika
    Astra-Zeneca, Mölndal.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences.
    Melgar, Silvia
    Astra-Zeneca, Mölndal.
    Jansson, Liselotte
    Astra-Zeneca, Mölndal.
    Predicting and monitoring colitis development in mice by micro-computed tomography2008In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 14, no 4, p. 491-499Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Computed tomography (CT) has been developed as a tool for monitoring human inflammatory bowel disease (IBD). The aim of this study was to evaluate colon wall thickness as a noninvasive marker in the dextran sodium sulfate (DSS) mouse model of colitis using micro-CT. METHODS: Mice were examined by micro-CT 1, 2, or 4 times between day 0 (d0) and d26 after induction of colitis to document the kinetics of changes in colon wall thickness and its relation to colitis development. RESULTS: DSS-treated mice displayed a significantly thicker colon wall at all timepoints (days 5, 8, 12, 19, and 26) investigated compared to healthy controls. Colon wall thickness showed a good correlation to the macroscopic grading of colitis (r = 0.81). The increase in colon wall thickness occurred mainly during the acute phase of colitis (between days 5 and 12) and did not progress much further in the chronic phase of colitis (d26). Colon wall thickness at d26 was thereby predicted by measurements at d12. All mice did not respond equally to DSS and this difference was manifest during the first 2 weeks of colitis, providing an important tool in stratifying responders from nonresponders. CONCLUSIONS: While the potential impact of handling and anesthesia should be considered on repeated micro-CT, irradiation exposure during repeated micro-CT did not affect the development of colitis. Thus, the results suggest that micro-CT can be used for monitoring and prediction of the inflammatory response in mouse colitis in future therapeutic studies.

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