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  • 1. Amcoff, K.
    et al.
    Joossens, M.
    Pierik, M. J.
    Jonkers, D.
    Bohr, J.
    Joossens, S
    Romberg-Camp, M.
    Nyhlin, Nils
    Wickbom, A.
    Rutgeerts, P. J.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bodin, L.
    Colombel, J. F.
    Vermeire, S.
    Halfvarson, Jonas
    Arvets inverkan på serologiska markörer hos tvillingar med IBD2012In: Gastrokuriren, ISSN 1651-0453, Vol. 17, no 26, p. MP-06-MP-06Article in journal (Other academic)
  • 2. Amcoff, Karin
    et al.
    Joossens, Marie
    Pierik, Marie J.
    Jonkers, Daisy
    Bohr, Johan
    Joossens, Sofie
    Romberg-Camps, Marielle
    Nyhlin, Nils
    Wickbom, Anna K.
    Rutgeerts, Paul J.
    Tysk, Curt
    Bodin, Lennart
    Colombel, Jean-Frederic
    Vermeire, Severine
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Influence of genetics in the expression of serological markers in twins with IBD2012In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 142, no 5, p. S881-S881Article in journal (Other academic)
  • 3.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Marie
    Department of Microbiology and Immunology, Rega Institute, Katholieke Universiteit, Leuven,Belgium; VIB Center for the Biology of Disease, Leuven, Belgium; Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit, Brussels, Belgium.
    Pierik, Marie J.
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Jonkers, Daisy
    Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
    Bohr, Johan
    Örebro University, School of Health Sciences. Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Sofie
    Gastroenterology, Catholic University of Leuven (KUL), Leuven, Belgium.
    Romberg-Camps, Mariëlle
    Department of Gastroenterology-Hepatology, Zuyderland Medical Center, Sittard, Netherlands.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Rutgeerts, Paul J.
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Tysk, Curt
    Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
    Colombel, Jean-Frederic
    Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York NY, USA.
    Vermeire, Severine
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed)
    Abstract [en]

    Background and Aims: An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.

    Methods: In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.

    Results: All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.

    Conclusions: We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.

  • 4.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Mikroskopisk kolit2008In: Medicinska mag- och tarmsjukdomar / [ed] Nyhlin, Henry, Lund: Studentlitteratur , 2008, 1, p. 351-357Chapter in book (Other academic)
  • 5. Bohr, Johan
    et al.
    Löfberg, Robert
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Microscopic colitis: collagenous and lymphocytic colitis2010In: Evidence-based gastroenterology and hepatology / [ed] John McDonald, Andrew Burroughs, Brian Feagan, M. Brian Fennerty, Wiley-Blackwell, 2010, 3, p. 257-266Chapter in book (Refereed)
  • 6.
    Bohr, Johan
    et al.
    Örebro University, School of Health and Medical Sciences.
    Nyhlin, N.
    Eriksson, S.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Mikroskopisk kolit hos äkta makar2008In: Gastrokuriren, Vol. 13, no 30, p. PO-09Article in journal (Other academic)
  • 7.
    Bohr, Johan
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Hegedus, Agnes
    Department of Laboratory Medicine/Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Diagnosis and management of microscopic colitis: Current perspectives2014In: Clinical and Experimental Gastroenterology, ISSN 1178-7023, E-ISSN 1178-7023, Vol. 7, p. 273-284Article, review/survey (Refereed)
    Abstract [en]

    Collagenous colitis and lymphocytic colitis, together constituting microscopic colitis, are common causes of chronic diarrhea. They are characterized clinically by chronic nonbloody diarrhea and a macroscopically normal colonic mucosa where characteristic histopathological findings are seen. Previously considered rare, they now have emerged as common disorders that need to be considered in the investigation of the patient with chronic diarrhea. The annual incidence of each disorder is five to ten per 100,000 inhabitants, with a peak incidence in 60- to 70-year-old individuals and a predominance of female patients in collagenous colitis. The etiology and pathophysiology are not well understood, and the current view suggests an uncontrolled mucosal immune reaction to various luminal agents in predisposed individuals. Clinical symptoms comprise chronic diarrhea, abdominal pain, fatigue, weight loss, and fecal incontinence that may impair the patient's health-related quality of life. An association is reported with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. The best-documented treatment, both short-term and long-term, is budesonide, which induces clinical remission in up to 80% of patients after 8 weeks' treatment. However, after successful budesonide therapy is ended, recurrence of clinical symptoms is common, and the best possible long-term management deserves further study. The long-term prognosis is good, and the risk of complications, including colonic cancer, is low. We present an update of the epidemiology, pathogenesis, diagnosis, and management of microscopic colitis.

  • 8.
    Carstens, Adam
    et al.
    Örebro University, School of Medical Sciences. Department of Internal Medicine, Ersta Hospital, Stockholm, Sweden; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Dicksved, Johan
    Department of Animal Nutrition and Management, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Nelson, Ronald
    Department of Clinical Sciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Lindqvist, Carl Mårten
    Örebro University, School of Medical Sciences.
    Andreasson, Anna
    Division of Family Medicine and Primary Care, Karolinska Institutet, Huddinge, Sweden.
    Bohr, Johan
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Gastroenterology.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Talley, Nicholas J.
    Faculty of Medicine and Health, University of Newcastle, Newcastle, Australia.
    Agréus, Lars
    Division of Family Medicine and Primary Care, Karolinska Institutet, Huddinge, Sweden.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Solna, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis2019In: Clinical and Translational Gastroenterology, ISSN 2155-384X, E-ISSN 2155-384X, Vol. 10, no 7, article id e00065Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: In inflammatory bowel disease (IBD), an aberrant immune response to gut microbiota is important, but the role of the microbiota in collagenous colitis (CC) is largely unknown. We aimed to characterize the microbiota of patients with CC compared with that of healthy control and patients with IBD.

    METHODS: Fecal samples were collected from patients with CC (n = 29), age- and sex-matched healthy controls (n = 29), patients with Crohn's disease (n = 32), and patients with ulcerative colitis (n = 32). Sequence data were obtained by 454 sequencing of 16S rRNA gene amplicons, and the obtained sequences were subsequently taxonomically classified.

    RESULTS: Analysis of similarity statistics showed a segregation between patients with CC and healthy controls with increasing taxonomic resolution, becoming significant comparing operational taxonomic unit data (P = 0.006). CC had a lower abundance of 10 different taxa. Taxa-specific analyses revealed a consistent lower abundance of several operational taxonomic units belonging to the Ruminococcaceae family in patients with CC, q < 0.05 after false discovery rate correction. Loss of these taxa was seen in patients with CC with active disease and/or corticosteroid treatment only and resembled the findings in patients with IBD.

    DISCUSSION: CC is associated with a specific fecal microbiome seen primarily in patients with active disease or ongoing corticosteroid treatment, whereas the microbiome of CC patients in remission resembled that of healthy controls. Notably, the shift in key taxa, including the Ruminococcaceae family, was also observed in IBD. There may be common mechanisms in the pathogenesis of CC and IBD.

  • 9.
    Edling, Lars
    et al.
    Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Rathsman, Sandra
    Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Sune
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University Hospital. Division of Gastroenterology.
    Celiac disease and giardiasis: a case report2012In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 24, no 8, p. 984-987Article in journal (Refereed)
    Abstract [en]

    When investigating a patient with suspected celiac disease (CD), several other conditions must be considered, including potential infection with Giardia lamblia. Although giardiasis is rare, its histopathological and serological picture may resemble that of CD. We report the case of a young man with diabetes mellitus and a family history of CD referred to our hospital because of diarrhoea and weight loss. Investigation showed, among other factors, partial villous atrophy in duodenal biopsies and elevated immunoglobulin A antitissue transglutaminase antibodies. The patient was diagnosed with CD and recommended a gluten-free diet. At the same time, faecal tests were conducted, indicating the presence of G. lamblia. The patient was treated and improved, even after discontinuing the gluten-free diet. Subsequent follow-up after 6 months showed total regression of mucosal histopathology and a normal antitissue transglutaminase antibodies level. Eur J Gastroenterol Hepatol 24:984-987 (c) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

  • 10.
    Fransén, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Franzén, Petra
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Magnuson, Anders
    Örebro University Hospital, Örebro, Sweden.
    Elmabsout, Ali
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University Hospital.
    Wickbom, Anna
    Örebro University Hospital, Örebro, Sweden.
    Curman, Bengt
    Örebro University Hospital, Örebro, Sweden.
    Törkvist, Leif
    Karolinska University Hospital, Stockholm, Sweden.
    D'Amato, Mauro
    Karolinska University Hospital, Stockholm, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Sirsjö, Allan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital.
    Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's disease2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, p. e72739-Article in journal (Refereed)
    Abstract [en]

    Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.

  • 11.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Institute of Infection, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, United Kingdom.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Tysk, Curt
    Örebro University Hospital. Division of Gastroenterology, Department of Medicine, Örebro University, Örebro, Sweden.
    Hultgren, Olof
    Örebro University Hospital.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment2015In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 132458Article in journal (Refereed)
    Abstract [en]

    Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhea. Various immune cell infiltrations in the epithelium and lamina propria are seen in MC immunopathology. We compared gene and protein expressions of different immune cell attracting chemokines and their receptors in colon biopsies from MC patients in active disease or histopathological remission (CC/LC-HR) with controls, using qRT-PCR and Luminex, respectively. CC and LC patients with active disease demonstrated a mixed chemokine profile with significantly enhanced gene and/or protein expressions of the chemokines CCL2, CCL3, CCL4, CCL5, CCL7, CCL22, CXCL8, CXCL9, CXCL10, CXCL11, and CX(3)CL1 and the receptors CCR2, CCR3, CCR4, CXCR1, CXCR2, and CX(3)CR1. Enhanced chemokine/chemokine receptor gene and protein levels in LC-HR patients were similar to LC patients, whereas CC-HR patients demonstrated almost normalized levels. These findings expand the current understanding of the involvement of various immune cells in MC immunopathology and endorse chemokines as potential diagnostic markers as well as therapeutic candidates. Moreover, this study further supports the hypothesis that CC and LC are two different entities due to differences in their immunoregulatory responses.

  • 12.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Increased expression of T cell recruiting chemokines in the colonic mucosa of microscopic colitis patients2013In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 135-135Article in journal (Other academic)
  • 13.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kumawat, Ashok
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    IL-1/TLR signaling inhibitors in microscopic and ulcerative colitis: Immunopathogenic markers of active disease and remission2013In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 167-167Article in journal (Other academic)
  • 14.
    Gunaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medicine, Div. of Gastroenterol., Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Department of Medicine, Div of Gastroenterol, Örebro Univ Hosp, Örebro, Sweden; Fac of Med and Hlth, Örebro Univ, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medical Sciences. Department of Microbiology and Immunology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.
    Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis2017In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.

    Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.

    Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.

    Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.

  • 15. Göranzon, C.
    et al.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Kumawat, Ashok Kumar
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Eriksson, J.
    Bohr, J.
    Nyhlin, Nils
    Immunohistokemisk karakterisering av lymfocyter vid microscopisk kolit2011In: Gastrokuriren, ISSN 1651-0453, Vol. 16, no 29, p. PO16-PO16Article in journal (Other academic)
  • 16. Göranzon, C.
    et al.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Kumawat, Ashok Kumar
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Eriksson, S.
    Bohr, Johan
    Nyhlin, Nils
    Immunohistochemical characterization of lymphocytes in microscopic colitis2010Conference paper (Other academic)
  • 17.
    Göranzon, C.
    et al.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren-Hörnqvist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Eriksson, S.
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Nyhlin, Nils
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Immunohistochemical characterization of lymphocytes in microscopic colitis2013In: Journal of Crohn's and Colitis, ISSN 1197-4982, Vol. 7, no 10, p. e434-e442Article in journal (Refereed)
    Abstract [en]

    Background and Aims: Microscopic colitis (MC), encompassing the subgroups collagenous colitis (CC) and lymphocytic colitis (LC), is characterized by macroscopically normal or near-normal colonic mucosa, and an increased number of intraepithelial lymphocytes (IELs) and mononuclear cell infiltration in the underlying lamina propria (LP), in addition to an increased collagen layer in CC. This study aimed to characterize the inflammatory cells involved in mucosal inflammation, using immunohistochemistry.

    Methods Paraffin-embedded biopsies from 23 untreated patients with MC (CC = 13, LC = 10) and 17 controls were stained with antibodies against CD3, CD4, CD8, CD20, CD30, Foxp3, CD45RO and Ki67. Computerized image analysis was used to calculate areas of stained lymphocytes in the surface and crypt epithelia as well as in the LP.

    Results In CC and LC, an increase of predominantly CD8+ lymphocytes was seen in both the epithelium and the lamina propria, whereas a decreased amount of CD4+ lymphocytes was found in the lamina propria. CD45RO+ and Foxp3+ cells were more abundant in all areas in both patient groups compared to controls, as were CD20+ areas, although more scarce. Ki67+ areas were only more abundant in the epithelium, whereas CD30+ areas were more abundant in the lamina propria of both patient groups compared to controls.

    Conclusions This study confirms an increased amount of CD8+ lymphocytes in the epithelium. Lymphocytic proliferation and activation markers were more abundant, whereas a decreased amount of CD4+ lymphocytes was seen in the LP. Further studies are needed to reveal the underlying mechanism(s).

  • 18.
    Günaltay, Sezin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Kumawat, Ashok Kumar
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Differential expression of interleukin-1/Toll-like receptor signaling regulators in microscopic and ulcerative colitis2014In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 20, no 34, p. 12249-12259Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate Toll-like receptor (TLR) signaling regulators in microscopic and ulcerative colitis patients.

    METHODS: Total RNA and microRNA were isolated from fresh frozen colonic biopsies of non-inflamed controls and patients with active or in-remission collagenous colitis (CC), lymphocytic colitis (LC), or ulcerative colitis (UC). We compared expressions of interleukin-1 receptor-associated kinase (IRAK)-2, IRAK-M, interleukin (IL)-37, microRNA (miR)-146a, miR-155, and miR-21 using quantitative real time reverse transcription polymerase chain reaction.

    RESULTS: IRAK-M expression was increased in LC patients with active disease in histopathological remission (LC-HR; P = 0.02) and UC patients (P = 0.01), but no differences in IRAK-2 expression were detected compared to controls. miR-146a, -155 and -21 expressions were increased in LC-HR (P = 0.04, 0.07, and 0.004) and UC (P = 0.02, 0.04 and 0.03) patients. miR-146a and miR-21 expressions were significantly enhanced in UC patients compared to UC remission (UC-R; P = 0.01 and 0.04). Likewise, active CC patients showed significantly increased expression of miR-155 (P = 0.003) and miR-21 (P = 0.006). IL-37 expression was decreased in both CC (P = 0.03) and LC (P = 0.04) patients with a similar trend in UC patients but not statistically significant, whilst it was increased in UC-R patients compared to controls (P = 0.02) and active UC (P = 0.001).

    CONCLUSION: The identification of differentially expressed miRNAs, IL-37, and IRAK-M suggests different pathophysiologic mechanisms in various disease stages in LC, CC, and UC. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

  • 19.
    Günaltay, Sezin
    et al.
    Örebro University, School of Medical Sciences.
    Repsilber, Dirk
    Örebro University, School of Medical Sciences.
    Helenius, Gisela
    Örebro University, School of Medical Sciences.
    Nyhlin, Nils
    Örebro University, School of Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health Sciences.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Oligoclonal T cell receptor repertoire in colonic biopsies of microscopic and ulcerative colitis patientsManuscript (preprint) (Other academic)
  • 20. Hjortswang, Henrik
    et al.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Benoni, Cecilia
    Kilander, Anders
    Larsson, Lasse
    Vigren, Lina
    Ström, Magnus
    Defining clinical criteria for clinical remission and disease activity in collagenous colitis2009In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 15, no 12, p. 1875-1881Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Collagenous colitis is a chronic inflammatory bowel disease accompanied mainly by nonbloody diarrhea. The objectives of treatment are to alleviate the symptoms and minimize the deleterious effects on health-related quality of life (HRQOL). There is still no generally accepted clinical definition of remission or relapse. The purpose of this study was to analyze the impact of bowel symptoms on HRQOL and accordingly suggest criteria for remission and disease activity based on impact of patient symptoms on HRQOL.

    METHODS: The design was a cross-sectional postal survey of 116 patients with collagenous colitis. The main outcome measures were 4 HRQOL questionnaires: the Short Health Scale, the Inflammatory Bowel Disease Questionnaire, the Rating Form of IBD Patient Concerns, and the Psychological General Well-Being Index, and a 1-week symptom diary recording number of stools/day and number of watery stools/day.

    RESULTS: Severity of bowel symptoms had a deleterious impact on patients' HRQOL. Patients with a mean of >/=3 stools/day or a mean of >/=1 watery stool/day had a significantly impaired HRQOL compared to those with <3 stools/day and <1 watery stool/day.

    CONCLUSIONS: We propose that clinical remission in collagenous colitis is defined as a mean of <3 stools/day and a mean of <1 watery stool per day and disease activity to be a daily mean of >/=3 stools or a mean of >/=1 watery stool.

  • 21. Hjortswang, Henrik
    et al.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Benoni, Cecilia
    Vigren, Lina
    Kilander, Anders
    Larsson, Lasse
    Taha, Yesuf
    Strom, Magnus
    Health-related quality of life is impaired in active collagenous colitis2011In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 43, no 2, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Objectives: The characteristic clinical symptoms of collagenous colitis are non-bloody diarrhoea, urgency and abdominal pain. Treatment is aimed at reducing the symptom burden and the disease impact on patients' health-related quality of life. The objective of this study was to analyse health-related quality of life in patients with collagenous colitis. Methods: In a cross-sectional, postal HRQL survey, 116 patients with collagenous colitis at four Swedish hospitals completed four health-related quality of life questionnaires, two disease-specific (Inflammatory Bowel Disease Questionnaire and Rating Form of IBD Patient Concerns), and two generic (Short Form 36, SF-36, and Psychological General Well-Being, PGWB), and a one-week symptom diary. Demographic and disease-related data were collected. Results for the collagenous colitis population were compared with a background population controlled for age and gender (n = 8931). Results: Compared with a Swedish background population, patients with collagenous colitis scored significantly worse in all Short Form 36 dimensions (p < 0.01), except physical function. Patients with active disease scored worse health-related quality of life than patients in remission. Co-existing disease had an impact on health-related quality of life measured with the generic measures. Lower education level and shorter disease duration were associated with decreased well-being. Conclusion: Health-related quality of life was impaired in patients with collagenous colitis compared with a background population. Disease activity is the most important factor associated with impairment of health-related quality of life. Patients in remission have a health-related quality of life similar to a background population. (C) 2010 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.

  • 22.
    Kumawat, Ashok
    et al.
    Örebro University, School of Health and Medical Sciences.
    Elgbratt, Kristina
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Increased frequencies of Ki67+ proliferating and CD45RO+ memory CD8+ and CD4+8+ T lymphocytes in the intestinal mucosa of collagenous colitis patients2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 73, no 4, p. 374-374Article in journal (Refereed)
  • 23.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Elgbratt, Kristina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Region Örebro County, Örebro, sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Reduced T cell receptor excision circle levels in the colonic mucosa of microscopic colitis patients indicate local proliferation rather than homing of peripheral lymphocytes to the inflamed mucosa2013In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 408638Article in journal (Refereed)
    Abstract [en]

    Dysregulated T cell responses in the intestine may lead to chronic bowel inflammation such as collagenous colitis (CC) and lymphocytic colitis (LC), together known as microscopic colitis (MC). Having demonstrated increased local T cell responses in the intestinal mucosa of MC patients, we investigated the recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic biopsies from CC (n = 8), LC (n = 5), and CC or LC patients in histopathological remission (CC-HR, n = 3) (LC-HR, n = 6), non-inflamed diarrhoea patients (n = 17), and controls (n = 10) by real-time PCR. We observed lower median TREC levels in both CC and LC patients as well as in LC-HR patients compared to controls. In contrast to MC patients, non-inflamed diarrhoea patients presented with enhanced TREC levels compared to controls. None of the recorded differences did, however, reach statistical significance. A trend towards increased relative expression of CD3 was noted in all MC subgroups examined and reached statistical significance in LC patients compared to controls. In conclusion, reduced TRECs level in the colonic mucosa, together with our previously demonstrated enhanced expression of Ki67(+) T cells, suggests local expansion of resident T lymphocytes in the inflamed mucosa of MC patients.

  • 24.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Elgbratt, Kristina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Reduced T cell receptor excision circle (TREC) levels in the colonic mucosa of microscopic colitis patients indicate local proliferation rather than homing of peripheral lymphocytes to the inflamed mucosaManuscript (preprint) (Other academic)
    Abstract [en]

    Aims: Dysregulated T cell responses in the intestine may lead to chronic bowel inflammation such as collagenous colitis (CC) and lymphocytic colitis (LC), together known as microscopic colitis (MC). Having demonstrated increased local T cell responses in the intestinal mucosa of MC patients, we investigated the recent thymic emigrants by measuring T cell receptor excision circle (TREC) levels in the colonic mucosa of CC and LC patients.

    Methods: Mucosal biopsies from CC (n=8), LC (n=5), and CC or LC patients in histopathological remission, (CC-HR, n=3), (LC-HR, n=6), non-inflamed diarrhoea patients (n=17) and controls (n=10) were analysed for TRECs expression by real time PCR.

    Results: The median TREC levels were lower in both CC and LC patients as well as in LCHR patients compared to controls. In contrast to MC patients, non-inflamed diarrhoea patients presented with enhanced TREC levels compared to controls. None of the recorded differences did however reach statistical significance. No differences were observed in median TREC levels in either CC-HR or LC-HR patients compared to active CC and LC patients. A trend towards increased relative expression of CD3 was noted in all MC subgroups examined; and reached statistical significance in LC patients compared to controls. LC patients had ignificantly increased CD3 mRNA levels also compared to CC, CC-HR, LC-HR and non-inflamed iarrhoea patients.

    Conclusions: Reduced TRECs level in the colonic mucosa, together with our previously demonstrated enhanced expression of Ki67+ T cells, suggest local expansion of resident T lymphocytes in the inflamed mucosa of MC patients.

  • 25.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Nyhlin, Nils
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University Hospital. Department of Microbiology and Immunology, Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    An In Vitro Model to Evaluate the Impact of the Soluble Factors from the Colonic Mucosa of Collagenous Colitis Patients on T Cells: Enhanced Production of IL-17A and IL-10 from Peripheral CD4(+) T Cells2014In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 879843Article in journal (Refereed)
    Abstract [en]

    Soluble factors from intestinal mucosal cells contribute to immune homeostasis in the gut. We have established an in vitro model to investigate the regulatory role of soluble factors from inflamed intestinal mucosa of collagenous colitis (CC) patients in the differentiation of T cells. Peripheral blood CD4(+) T cells from healthy donors were polyclonally activated in the presence of conditioned medium (CM) generated from denuded biopsies (DNB) or isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients compared to noninflamed controls, to determine proliferation and secretion of cytokines involved in T-cell differentiation. Compared to controls, we observed significantly increased production of the proinflammatory cytokines IFN-gamma, IL-17A, IL-6, and IL-1 beta and the anti-inflammatory cytokines IL-4 and IL-10 in the presence of CC-DNB-CM. The most pronounced effect of CC-LPMC-CM on peripheral CD4(+) T cells was a trend towards increased production of IL-17A and IL-10. A trend towards reduced inhibition of T-cell proliferation was noted in the presence of CC-DNB-CM. In conclusion, our in vitro model reveals implications of soluble factors from CC colonic mucosa on peripheral T cells, enhancing their production of both pro-and anti-inflammatory cytokines.

  • 26. Kumawat, Ashok Kumar
    et al.
    Strid, H.
    Elgbratt, K.
    Nyhlin, Nils
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, J.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Collagenous colitis patients demonstrate a Th1/CTL-associated gene expression profile with increased frequencies of Ki67+ proliferating and CD45RO+ activated/ memory CD8+ and CD4+8+ mucosal T cells2011Conference paper (Other academic)
  • 27. Kumawat, Ashok Kumar
    et al.
    Strid, H.
    Elgbratt, K.
    Nyhlin, Nils
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, J.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences.
    Collagenous colitis patients demonstrate a Th1/CTL-associated gene expression profile with increased frequencies of Ki67+ proliferating and CD45RO+ activated/memory CD8+ and CD4+8+ mucosal T cells2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl. 3, p. A318-Article in journal (Refereed)
  • 28. Kumawat, Ashok Kumar
    et al.
    Strid, H.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Patienter med mikroskopisk kolit har blandad Th1/Th17 samt CTL-associerad cytokinprofil2012Conference paper (Other academic)
  • 29.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Elgbratt, Kristina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept. of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept. of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Hultgren Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    Microscopic colitis patients have increased frequencies of Ki67+proliferating and CD45RO+ active/memory CD8+ and CD4+8mucosal T cells2013In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 7, no 9, p. 694-705Article in journal (Refereed)
    Abstract [en]

    Background: Collagenous colitis (CC) and lymphocytic colitis (LC) are chronic inflammatory bowel disorders of unknown etiology. This study investigated phenotypic characteristics of the mucosal lymphocytes in CC and LC.

    Methods: Lamina propria and intraepithelial lymphocytes (LPLs, IELs) isolated from mucosal biopsies from CC (n = 7), LC (n = 6), as well as LC or CC patients in histopathological remission, (LC-HR) (n = 6) and CC-HR (n = 4) and non-inflamed controls (n = 10) were phenotypically characterized by four-color flow cytometry.

    Results: The proportions of CD8+ IELs were increased in CC and LC (p < 0.01) compared to controls. Increased proportions of CD45RO+CD8+ IELs and LPLs were observed in LC and even more in CC patients (p < 0.01). Both CC (p < 0.05) and LC patients had elevated proportions of CD4+8+ IELs and LPLs compared to controls. The proportions of CD45RO+ cells were increased in CD4+8+ IELs and LPLs (p < 0.05) in CC and LC patients compared to controls. Both CC (p < 0.05) and LC patients had higher proportions of Ki67+CD8+ IELs and LPLs compared to controls.

    In contrast, decreased proportions of CD4+ LPLs were observed in CC and LC as well as CD4+ IELs in LC compared to controls. Increased proportions of Ki67+CD4+ IELs and LPLs (p < 0.05) were observed in CC and LC patients. CC-HR but not LC-HR patients demonstrated normalized proportions of both IELs and LPLs compared to CC and LC patients respectively.

    Conclusion: LC and CC patients have differences in mucosal lymphocyte subsets, with increased proportions of Ki67+ and CD45RO+ CD8+ and CD4+8+ mucosal T cells.

  • 30.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences.
    Strid, Hilja
    Örebro University, School of Health and Medical Sciences.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital.
    Bohr, Johan
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Region Örebro County, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Health and Medical Sciences.
    Microscopic colitis patients demonstrate a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile2013In: Molecular Immunology, ISSN 0161-5890, E-ISSN 1872-9142, Vol. 55, no 3-4, p. 355-364Article in journal (Refereed)
    Abstract [en]

    Background:

    Microscopic colitis (MC) is a chronic inflammatory bowel disorder of unknown aetiology comprising collagenous colitis (CC) and lymphocytic colitis (LC). Data on the local cytokine profile in MC is limited. This study investigated the T helper (Th) cell and cytotoxic T lymphocyte (CTL) mucosal cytokine profile at messenger and protein levels in MC patients.

    Methods:

    Mucosal biopsies from CC (n = 10), LC (n = 5), and CC or LC patients in histopathological remission (CC-HR, n = 4), (LC-HR, n = 6), ulcerative colitis (UC, n = 3) and controls (n = 10) were analysed by real-time PCR and Luminex for expression/production of IL-1 beta, -4, -5, -6, -10, -12, -17, -21, -22, -23, IFN-gamma, TNF-alpha, T-bet and RORC2.

    Results:

    Mucosal mRNA but not protein levels of IFN-gamma and IL-12 were significantly up regulated in CC, LC as well as UC patients compared to controls. Transcription of the Th1 transcription factor T-bet was significantly enhanced in CC but not LC patients. mRNA levels for IL-17A, IL-21, IL-22 and IL-6 were significantly up regulated in CC and LC patients compared to controls, albeit less than in UC patients. Significantly enhanced IL-21 protein levels were noted in both CC and LC patients. IL-6 protein and IL-1 beta mRNA levels were increased in CC and UC but not LC patients. Increased mucosal mRNA levels of IFN-gamma, IL-21 and IL-22 were correlated with higher clinical activity, recorded as the number of bowel movements per day, in MC patients.

    Although at lower magnitude, IL-23A mRNA was upregulated in CC and LC, whereas TNF-alpha protein was increased in CC, LC as well as in UC patients.

    Neither mRNA nor protein levels of IL-4, IL-5 or IL-10 were significantly changed in any of the colitis groups. LC-HR and especially CC-HR patients had normalized mRNA and protein levels of the above cytokines compared to LC and CC patients. No significant differences were found between LC and CC in cytokine expression/production.

    Conclusion:

    LC and CC patients demonstrate a mixed Th17/Tc17 and Th1/Tc1 mucosal cytokine profile.

  • 31.
    Kumawat, Ashok Kumar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren, Olof
    Örebro University, School of Medicine, Örebro University, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    An in vitro model for analysis of the impact of the colonic milieu in collagenous colitis patients on peripheral T lymphocyte activation and differentiationManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Soluble factors released by intestinal mucosal cells contribute to immune homeostasis in the gut. This is the first study to investigate the role of soluble factors from the intestinal mucosa of collagenous colitis (CC) patients in the regulation of effector T cells using a novel system that mimics the in vivo exposure of newly recruited peripheral blood T cells to soluble factors derived from the colonic milieu of normal individuals and inflamed CC patient mucosa.

    Methods: Denuded biopsies (DNB) and isolated lamina propria mononuclear cells (LPMCs) from mucosal biopsies from CC patients and non-inflamed controls were cultured to collect conditioned medium (CM). Enriched peripheral blood CD4+ T cells from healthy donors were polyclonally activated in the absence or presence of CM from CC patients and controls. Proliferation, as well as secretion of IL-1β IL-4, IL-6, IL-10, IL-17A, IFN-γ and TNF-α was analysed the latter with Luminex® analysis.

    Results: Peripheral CD4+ T cells exposed to CM from the colonic mucosa demonstrated reduced proliferation. This inhibition was less pronounced with DNB-CM derived from CC patients compared to non-inflamed control mucosa. In contrast, LPMC-CM from non-inflamed controls inhibited T-cell proliferation less than LPMC-CM from CC patients. Both DNB-CM and LPMC-CM from CC patients induced more or less increased production of the proinflammatory cytokines IFN-γ, IL-17A, IL-6 and TNF-α as well as the anti-inflammatory cytokines IL-4 and IL-10 from peripheral CD4+ T cells compared to non-inflamed controls. In contrast, IL-1β production by peripheral T cells showed mixed results – it was either increased or reduced in the presence of both DNB and LPMC-CM from CC patients compared to noninflamed controls with different blood donors and different concentrations.

    Conclusion: Our preliminary data indicates reduced inhibition of proliferation of peripheral CD4+ T cells in the presence of mucosa-derived soluble factors from CC patients compared to controls. In addition, increased production of both inflammatory and anti-inflammatory cytokines by peripheral CD4+ T cells was recorded in the presence of soluble factors from the colonic mucosa of CC patients compared to controls. This model can be valuable in evaluating the effect(s) of existing and new drugs on T cell differentiation in the intestinal mucosa.

  • 32.
    Kumawat, Ashok
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University Hospital, Örebro, Sweden.
    Hultgren, Olof
    Örebro University Hospital, Örebro, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medicine, Örebro University, Sweden.
    An in vitro model for analysis of the impact of the colonic milieu in collagenous colitis patients on peripheral T lymphocyte activation and differentiation2013In: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, p. 168-168Article in journal (Other academic)
  • 33.
    Munch, Andreas
    et al.
    Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Bohr, Johan
    Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Miehlke, Stephan
    Centre for Digestive Disease, Hamburg, Germany.
    Benoni, Cecilia
    Department of Gastroenterology, University Hospital, Malmö, Sweden.
    Olesen, Martin
    Department of Pathology, University Hospital, Malmö, Sweden.
    Öst, Åke
    Department of Pathology and Cytology, Aleris Medilab, Täby, Sweden.
    Strandberg, Lars
    Regional Hospital, Falun, Sweden.
    Hellström, Per M.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hertervig, Erik
    Department of Gastroenterology, University Hospital, Lund, Sweden.
    Armerding, Peter
    Gastroenterology, Private Practice, Berlin, Germany.
    Stehlik, Jiri
    Department of Gastroenterology, Regional Hospital, Usti nad Labem, Czech Republic.
    Lindberg, Greger
    Centre for Digestive Diseases, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Björk, Jan
    Centre for Digestive Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
    Lapidus, Annika
    Department of Gastroenterology, Ersta Hospital, Stockholm, Sweden.
    Löfberg, Robert
    IBD Unit, Department of Gastroenterology, Sophiahemmet, Stockholm, Sweden.
    Bonderup, Ole
    Department of Gastroenterology, Regional Hospital, Silkeborg, Denmark.
    Avnström, Sören
    Department of Gastroenterology, Amager Hospital, Copenhagen, Denmark.
    Rössle, Martin
    Gastroenterology, Private Practice, Freiburg, Germany.
    Dilger, Karin
    Dr Falk Pharma GmbH, Freiburg, Germany.
    Mueller, Ralph
    Dr Falk Pharma GmbH, Freiburg, Germany.
    Greinwald, Roland
    Dr Falk Pharma GmbH, Freiburg, Germany.
    Tysk, Curt
    Örebro University Hospital. Department of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Ström, Magnus
    Division of Gastroenterology and Hepatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Low-dose budesonide for maintenance of clinical remission in collagenous colitis: a randomised, placebo-controlled, 12-month trial2016In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 65, no 1, p. 47-56Article in journal (Refereed)
    Abstract [en]

    Objective: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.

    Design: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.

    Results: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), p<0.001). Health-related quality of life was maintained during the 12-month double-blind phase in budesonide-treated patients. During treatment-free follow-up, 82.1% (23/28 patients) formerly receiving budesonide relapsed after study drug discontinuation. Low-dose budesonide over 1 year resulted in few suspected adverse drug reactions (7/44 patients), all non-serious.

    Conclusions: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.

  • 34.
    Münch, A.
    et al.
    Faculty of Health Science, Linköping University, Linköping, Sweden.
    Aust, D.
    Department of Pathology, University Hospital, Dresden, Germany.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Bonderup, O.
    Diagnostic Center, Division of Gastroenterology, Regional Hospital, Silkeborg, Denmark.
    Bañares, F. Fernández
    Department of Gastroenterology, Hospital Universitari Mutua Terrassa, University of Barcelona, Terrassa, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas CIBERehd,Terrassa, Spain.
    Hjortswang, H.
    Faculty of Health Science, Linköping University, Linköping, Sweden.
    Madisch, A.
    Medical Department I, Academic Teaching Hospital Siloah, Hannover, Germany.
    Munck, L. K.
    Departement of Gastroenterology, Køge University Hospital, Køge, Denmark.
    Ström, M.
    Faculty of Health Science, Linköping University, Linköping, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Miehlke, S.
    Center for Digestive Disease, Cooperation of Internal Medicine, Hamburg, Germany.
    Microscopic colitis: current status, present and future challenges statements of the European microscopic colitis group2012In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 6, no 9, p. 932-945Article in journal (Refereed)
    Abstract [en]

    Microscopic colitis (MC) is an inflammatory bowel disease presenting with chronic, non-bloody watery diarrhoea and few or no endoscopic abnormalities. The histological examination reveals mainly two subtypes of MC, lymphocytic or collagenous colitis. Despite the fact that the incidence in MC has been rising over the last decades, research has been sparse and our knowledge about MC remains limited. Specialists in the field have initiated the European Microscopic Colitis Group (EMCG) with the primary goal to create awareness on MC. The EMCG is furthermore a forum with the intention to promote clinical and basic research. In this article statements and comments are given that all members of the EMCG have considered being of importance for a better understanding of MC. The paper focuses on the newest updates in epidemiology, symptoms and diagnostic criteria, pathophysiology and highlights some unsolved problems. Moreover, a new treatment algorithm is proposed on the basis of new evidence from well-designed, randomized control trials.

  • 35. Münch, A.
    et al.
    Bohr, J.
    Vigren, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Ström, M.
    Methotrexate is not effective in budesonide-refractory collagenous colitis2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl 3, p. A406-A406Article in journal (Refereed)
  • 36. Münch, A.
    et al.
    Bohr, J.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Vigren, L.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ström, M.
    Metotrexat vid budesonidrefraktär kollagen kolit2012In: Gastrokuriren, ISSN 1651-0453, Vol. 17, no 34, p. PO-15-PO-15Article in journal (Other academic)
  • 37.
    Münch, Andreas
    et al.
    Department of Gastroenterology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden .
    Tysk, Curt
    Faculty of Medicine and Health, School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health Sciences. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Madisch, Ahmed
    Medical Department I, Siloah Hospital, Hannover, Germany.
    Bonderup, Ole K.
    Diagnostic Center, Silkeborg Hospital, Silkeborg, Denmark.
    Mohrbacher, Ralf
    Research & Development, Dr Falk Pharma GmbH, Freiburg, Germany.
    Mueller, Ralph
    Research & Development, Dr Falk Pharma GmbH, Freiburg, Germany.
    Greinwald, Roland
    Research & Development, Dr Falk Pharma GmbH, Freiburg, Germany.
    Ström, Magnus
    Department of Gastroenterology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Miehlke, Stephan
    Center for Digestive Diseases, Cooperation of Internal Medicine, Hamburg, Germany.
    Smoking Status Influences Clinical Outcome in Collagenous Colitis2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 4, p. 449-454Article in journal (Refereed)
    Abstract [en]

    Background: The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known.

    Methods: In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model.

    Results: Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome.

    Conclusion: Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data.

  • 38. Nyhlin, N.
    et al.
    Bergman, J.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Gustavsson, A.
    Halfvarson, Jonas
    Salén, E.
    Sandberg Gertzén, H.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Plasmaferes vid svår läkemedelsutlöst kolestas2008In: Gastrokuriren, Vol. 13, no 33, p. PO-16Article in journal (Other (popular science, discussion, etc.))
  • 39. Nyhlin, Nils
    et al.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Eriksson, Sune
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Microscopic colitis: a common and an easily overlooked cause of chronic diarrhoea2008In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 19, no 3, p. 181-186Article in journal (Refereed)
    Abstract [en]

    Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is characterised clinically by chronic watery diarrhoea, a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4–6/100,000 inhabitants, with a peak incidence in 60–70 year old individuals and a noticeable female predominance in collagenous colitis. The aetiology is unknown. Abdominal pain, weight loss, fatigue, and faecal incontinence are common symptoms in addition to chronic diarrhoea that impair the health-related quality of life of the patient. There is an association to other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.

  • 40. Nyhlin, Nils
    et al.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Brummer, Robert
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Wickbom, Anna
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Abdominal pain is common in microscopic colitis despite remission: a long-term follow-up of 203 patients2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57, no suppl IArticle in journal (Other academic)
  • 41.
    Nyhlin, Nils
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Letter: persisting clinical symptoms in microscopic colitis in remission - authors' reply2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 40, no 1, p. 118-118Article in journal (Refereed)
  • 42.
    Nyhlin, Nils
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Wickbom, Anna
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Tysk, Curt
    Örebro University Hospital. Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Long-term prognosis of clinical symptoms and health-related quality of life in microscopic colitis: a case-control study2014In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 39, no 9, p. 963-972Article in journal (Refereed)
    Abstract [en]

    Background: Microscopic colitis, comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a common cause of chronic diarrhoea. The long-term prognosis is not well described.

    Aim: To study outcome of symptoms and health-related quality of life (HRQoL).

    Methods: A case-control study using a postal questionnaire with three population-based controls per patient matched for age, sex and municipality. HRQoL was assessed by the Short Health Scale (SHS). Patients in clinical remission, defined as a mean of <3 stools/day, were evaluated separately (CC; n=72, LC; n=60).

    Results: The study included 212 patients and 627 matched controls. Median disease duration was 5.9 (range 0.5-27) years and 6.4 (0.3-14.8) years for CC and LC respectively. Abdominal pain, fatigue, arthralgia, myalgia, faecal incontinence and nocturnal defecation were significantly more prevalent in CC patients compared with controls. These differences persisted in CC patients in clinical remission with respect to abdominal pain (36% vs. 21%), fatigue (54% vs. 34%), arthralgia (61% vs. 41%) and myalgia (53% vs. 37%). In LC patients, abdominal pain, fatigue, faecal incontinence and nocturnal defecation were more prevalent compared with controls. In LC patients in clinical remission, fatigue was more prevalent compared with controls (54% vs. 37%). These differences were statistically significant (P<0.05). All four HRQoL dimensions (symptom burden, social function, disease-related worry, general well-being) were impaired in patients with active CC and LC.

    Conclusions: Although considered to be in clinical remission, patients with microscopic colitis suffer from persisting symptoms such as abdominal pain, fatigue, arthralgia or myalgia several years after diagnosis.

  • 43. Strid, H.
    et al.
    Kumawat, Ashok Kumar
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Altered gene expression of IL-6 and rennin in colonic biopsies from collagenous colitis and ulcerative colitis compared to healthy controls2011In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 60, no Suppl. 3, article id A317Article in journal (Refereed)
  • 44. Strid, Hilja
    et al.
    Kumawat, Ashok
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hultgren Hörnquist, Elisabet
    Örebro University, School of Medicine, Örebro University, Sweden.
    Bohr, Johan
    Genuttrycket för Renin och IL-6 i kolonmucosan är förändrad vid kollagen kolit2012Conference paper (Other academic)
  • 45.
    Tysk, Curt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Nyhlin, Nils
    Wickbom, Anna
    Eriksson, Sune
    Diagnosis and management of microscopic colitis2008In: World Journal of Gastroenterology, ISSN 1007-9327, E-ISSN 2219-2840, Vol. 14, no 48, p. 7280-7288Article in journal (Other academic)
    Abstract [en]

    Microscopic colitis, comprising collagenous and lymphocytic colitis, is characterized clinically by chronic watery diarrhea, and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100,000 inhabitants, with a peak incidence in 60-70-year-old individuals and a noticeable female predominance for collagenous colitis. The etiology is unknown. Chronic diarrhea, abdominal pain, weight loss, fatigue and fecal incontinence are common symptoms, which impair the health-related quality of life of the patient. There is an association with other autoimmune disorders such as celiac disease, diabetes mellitus, thyroid disorders and arthritis. Budesonide is the best-documented short-term treatment, but the optimal long-term strategy needs further study. The long-term prognosis is good and the risk of complications including colonic cancer is low.

  • 46.
    Tysk, Curt
    et al.
    Örebro University, School of Health and Medical Sciences.
    Wickbom, Anna
    Nyhlin, Nils
    Eriksson, Sune
    Bohr, Johan
    Recent advances in diagnosis and treatment of microscopic colitis2011In: Annals of Gastroenterology, ISSN 1108-7471, E-ISSN 1792-7463, Vol. 24, no 4, p. 253-262Article in journal (Other academic)
    Abstract [en]

    Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is a common cause of chronic diarrhoea. It is characterised clinically by chronic watery diarrhoea and a macroscopically normal colonic mucosa where diagnostic histopathological features are seen on microscopic examination. The annual incidence of each disorder is 4-6/100000 inhabitants, with a peak incidence in individuals 60-70 years old and a noticeable female predominance in collagenous colitis. The aetiology is unknown. Chronic diarrhoea, abdominal pain, weight loss, fatigue, and faecal incontinence are common symptoms that impair the health-related quality of life of the patient. There is an association with other autoimmune disorders, such as celiac disease, thyroid disorders, diabetes mellitus, and arthritis. Budesonide is the best-documented treatment, both short-term and long-term. Recurrence of symptoms is common after withdrawal of successful budesonide therapy, and the optimal long-term treatment strategy needs further study. The long-term prognosis is good, and the risk of complications including colonic cancer is low. We review epidemiology, clinical features, diagnosis and treatment of microscopic colitis,

  • 47. Vigren, L.
    et al.
    Sjöberg, K.
    Benoni, C.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Kilander, A.
    Larsson, L.
    Ström, M.
    Hjortswang, H.
    Rökning och kollagen kolit2011In: Gastrokuriren, ISSN 1651-0453, Vol. 16, no 29, p. PO-17-PO-17Article in journal (Other academic)
  • 48. Vigren, L.
    et al.
    Sjöberg, K.
    Benoni, C.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bohr, J.
    Kilander, A.
    Larsson, L.
    Ström, M.
    Hjortswang, H.
    Smoking habits in patients with collagenous colitis2010In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 59, no suppl 3, p. A182-A182Article in journal (Other academic)
  • 49.
    Vigren, Lina
    et al.
    Div Gastroenterol, Dept Clin Sci, Skåne Univ Hosp, Lund Univ, Malmö, Sweden.
    Sjöberg, Klas
    Div Gastroenterol, Dept Clin Sci, Skåne Univ Hosp, Lund Univ, Malmö, Sweden.
    Benoni, Cecilia
    Div Gastroenterol, Dept Clin Sci, Skåne Univ Hosp, Lund Univ, Malmö, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences.
    Kilander, Anders
    Dept Med, Div Gastroenterol, Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Larsson, Lasse
    Dept Med, Div Gastroenterol, Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Ström, Magnus
    Fac Hlth Sci, Dept Clin & Expt Med, Div Gastroenterol Inflammatory Med, Linköping Univ, Linköping, Sweden; Dept Gastroenterol & Endocrinol, Linköping Univ Hosp, Linköping, Sweden.
    Hjortswang, Henrik
    Fac Hlth Sci, Dept Clin & Expt Med, Div Gastroenterol Inflammatory Med, Linköping Univ, Linköping, Sweden; Dept Gastroenterol & Endocrinol, Linköping Univ Hosp, Linköping, Sweden.
    Is smoking a risk factor for collagenous colitis?2011In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 46, no 11, p. 1334-1339Article in journal (Refereed)
    Abstract [en]

    Objective. The association between smoking and idiopathic inflammatory bowel disease is well known; smoking seems to have a diverse effect. Crohn's disease is associated with smoking, while ulcerative colitis is associated with non-smoking. Data on smoking inmicroscopic colitis of the collagenous type (CC) are lacking. The aim of this investigation was to study smoking habits in CC and to observe whether smoking had any impact on the course of the disease. Materials and methods. 116 patients (92 women) with median age of 62 years (interquartile range 55-73) answered questionnaires covering demographic data, smoking habits and disease activity. As control group we used data from the general population in Sweden retrieved from Statistics Sweden, the central bureau for national socioeconomic information. Results. Of the 116 CC patients, 37% were smokers compared with 17% of controls (p < 0.001, odds ratio (OR) 2.95). In the age group 16-44 years, 75% of CC patients were smokers compared with 15% of controls (p < 0.001, OR 16.54). All CC smoker patients started smoking before the onset of disease. Furthermore, smokers developed the disease earlier than non-smokers - at 42 years of age (median) compared with 56 years in non-smokers (p < 0.003). Although the proportion with active disease did not differ between smokers and nonsmokers, there was a trend indicating that more smokers received active treatment (42% vs. 17%, p = 0.078). Conclusions. Smoking is a risk factor for CC. Smokers develop their disease more than 10 years earlier than non-smokers.

  • 50.
    Vigren, Lina
    et al.
    Department of Clinical Sciences, Division of Gastroenterology, Skåne University Hospital, Malmö, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Ström, Magnus
    Department of Clinical and Experimental Medicine, Division of Gastroenterology Within Inflammatory Medicine, Faculty of Health Sciences, Linköping, Sweden .
    Kilander, Anders F.
    Department of Medicine, Division of Gastroenterology, Sahlgrenska University Hospital, Gothenburg, Sweden .
    Hjortswang, Henrik
    Department of Clinical and Experimental Medicine, Division of Gastroenterology Within Inflammatory Medicine, Faculty of Health Sciences, Linkøping, Sweden.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Benoni, Cecilia
    Department of Clinical Sciences, Division of Gastroenterology, Skåne University Hospital, Malmö, Sweden .
    Larson, Lasse
    Department of Medicine, Division of Gastroenterology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Sjöberg, Klas
    Department of Clinical Sciences, Division of Gastroenterology, Skåne University Hospital, Malmö, Sweden.
    Celiac disease and other autoimmune diseases in patients with collagenous colitis2013In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, no 8, p. 944-950Article in journal (Refereed)
    Abstract [en]

    Background and aims. Collagenous colitis (CC) is associated with autoimmune disorders. The aim of the present study was to investigate the relationship between CC and autoimmune disorders in a Swedish multicenter study. Methods. Patients with CC answered questionnaires about demographic data and disease activity. The patient's files were scrutinized for information about autoimmune diseases. Results. A total number of 116 CC patients were included; 92 women, 24 men, median age 62 years (IQR 55-73). In total, 30.2% had one or more autoimmune disorder. Most common were celiac disease (CeD; 12.9%) and autoimmune thyroid disease (ATD, 10.3%), but they also had Sjogren's syndrome (3.4%), diabetes mellitus (1.7%) and conditions in skin and joints (6.0%). Patients with associated autoimmune disease had more often nocturnal stools. The majority of the patients with associated CeD or ATD got these diagnoses before the colitis diagnosis. Conclusion. Autoimmune disorders occurred in one-third of these patients, especially CeD. In classic inflammatory bowel disease (IBD), liver disease is described in contrast to CC where no cases occurred. Instead, CeD was prevalent, a condition not reported in classic IBD. Patients with an associated autoimmune disease had more symptoms. Patients with CC and CeD had an earlier onset of their colitis. The majority of the patients with both CC and CeD were smokers. Associated autoimmune disease should be contemplated in the follow-up of these patients.

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