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  • 1.
    Almon, Ricardo
    et al.
    Örebro University, School of Health and Medical Sciences.
    Engfeldt, Peter
    Örebro University, School of Health and Medical Sciences.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Sjöström, Michael
    Nilsson, Torbjörn K.
    Örebro University, School of Health and Medical Sciences.
    Prevalence and trends in adult-type hypolactasia in different age cohorts in Central Sweden diagnosed by genotyping for the adult-type hypolactasia-linked LCT -13910C > T mutation2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 2, p. 165-170Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Adult-type hypolactasia (AtH) can be diagnosed by genotyping in addition to functional tests or intestinal biopsy. The aims of this study were to estimate the prevalence of AtH by genotyping and to investigate whether AtH prevalence has changed in Sweden during the 20th century. MATERIAL AND METHODS: Schoolchildren (n=690) born in 1983 and 1989, and elderly individuals (n=392) born between 1920 and 1932 were genotyped for AtH using Pyrosequencing technology. RESULTS: The overall prevalence of AtH among children was 14.1%. The majority of children (92%, n=635) were Caucasians with genotype prevalences: CC, 61 (10%); CT, 259 (41%); TT, 307 (49%). The frequency of the mutated allele q was 0.300 in this cohort. The prevalence of AtH estimated from the Hardy-Weinberg equilibrium (HWE) (q 2), was 9.0% (95% CI: 6.7-11.2%). Eight percent (n=55) of the children were non-Caucasian; genotype prevalences were CC, 36 (66%); CT, 15 (27%); TT, 4 (7%). The prevalence of AtH in these children estimated from HWE was 62.5% (95% CI: 49.7-75.3%). The elderly subjects were all Caucasians. Their genotype prevalences were: CC, 20 (5%); CT, 166 (42%); TT, 206 (53%); the frequency of the mutated allele q was 0.262 and their AtH prevalence estimated from HWE was 6.8% (95% CI: 4.3-9.2%). CONCLUSIONS: The overall prevalence of AtH in children (14%) was higher than previously thought. Among Caucasians, higher figures were seen in children than in the elderly (9% versus 6.8%). The prevalence thus seems to be increasing and this may be due to the immigration of both non-Caucasian and Caucasian groups with a higher prevalence of AtH.

  • 2. 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)
  • 3. 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)
  • 4.
    Amcoff, Karin
    et al.
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Joossens, Marie
    KU Leuven, Department of Microbiology and Immunology, Rega Institute, Herestraat 49, B-3000 Leuven, Belgium VIB, Center for the Biology of Disease, Herestraat 49, B-3000 Leuven, Belgium Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, 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.
    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.
    Wickbom, Anna
    Örebro University, School of Medical Sciences. Department of Gastroenterology.
    Rutgeerts, Paul J.
    Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
    Tysk, Curt
    Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, 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.
    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.

  • 5. Bodger, K.
    et al.
    Halfvarson, Jonas
    Dodson, A. R.
    Campbell, F.
    Wilson, S.
    Lee, R.
    Lindberg, E.
    Järnerot, G.
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Rhodes, J. M.
    Altered colonic glycoprotein expression in unaffected monozygotic twins of inflammatory bowel disease patients2006In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 55, no 7, p. 973-977Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND AIMS: Previous chromatographic analysis of colonic mucins from monozygotic twins with inflammatory bowel disease (IBD) suggested a genetic mucin alteration in ulcerative colitis (UC). This study explores this further by assessing mucosal expression of the oncofetal carbohydrate antigen TF (galactose beta1, 3 N-acetylgalactosamine alpha-), among the same IBD twins. MATERIALS AND METHODS: Formalin fixed paraffin embedded rectal biopsies were studied from 22 monozygotic twin pairs with IBD. These included eight UC twin pairs and 14 Crohn's disease (CD) twin pairs, with six pairs concordant for disease and 16 unaffected twin siblings. Closely adjacent sections were assessed by peanut lectin histochemistry for TF expression and immunohistochemically for nuclear factor kappaB (NFkappaB) activation with investigators blinded to the diagnosis. RESULTS: Unaffected twins were almost all TF positive (15/16) compared with 5/29 histologically normal controls (p<0.0001). Unaffected UC (7/8) and CD twins (8/8) were similarly TF positive. TF positivity was confined mainly to the superficial epithelium and absent from the stem cell compartment of the lower crypts, suggesting that glycosylation changes are acquired rather than genetically determined. Activated NFkappaB was present in the surface epithelium of mucosal biopsies from 13/14 unaffected IBD twins but in only 6/22 histologically normal controls (p=0.0004). All 22 affected IBD twins were TF positive and 18 were positive for activated NFkappaB. CONCLUSIONS: Altered mucosal glycosylation in unaffected identical twins of IBD patients was confirmed in this study. This occurred in both UC and CD twins. The changes are probably acquired rather than congenital and may reflect "preinflammatory" NFkappaB activation.

  • 6. 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)
  • 7.
    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)
  • 8. Dicksved, Johan
    et al.
    Halfvarson, Jonas
    Rosenquist, Magnus
    Järnerot, Gunnar
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Apajalahti, Juha
    Engstrand, Lars
    Jansson, Janet K.
    Molecular analysis of the gut microbiota of identical twins with Crohn's disease2008In: The ISME journal, ISSN 1751-7370, Vol. 2, no 7, p. 716-727Article in journal (Refereed)
    Abstract [en]

    Increasing evidence suggests that a combination of host genetics and the composition of the gut microbiota are important for development of Crohn's disease (CD). Our aim was to study identical twins with CD to determine microbial factors independent of host genetics. Fecal samples were studied from 10 monozygotic twin pairs with CD (discordant n=6 and concordant n=4) and 8 healthy twin pairs. DNA was extracted, 16S rRNA genes were PCR amplified and T-RFLP fingerprints generated using general bacterial and Bacteroides group-specific primers. The microbial communities were also profiled based on their percentage G+C contents. Bacteroides 16S rRNA genes were cloned and sequenced from a subset of the samples. The bacterial diversity in each sample and similarity indices between samples were estimated based on the T-RFLP data using a combination of statistical approaches. Healthy individuals had a significantly higher bacterial diversity compared to individuals with CD. The fecal microbial communities were more similar between healthy twins than between twins with CD, especially when these were discordant for the disease. The microbial community profiles of individuals with ileal CD were significantly different from healthy individuals and those with colonic CD. Also, CD individuals had a lower relative abundance of B. uniformis and higher relative abundances of B. ovatus and B. vulgatus. Our results suggest that genetics and/or environmental exposure during childhood, in part, determine the gut microbial composition. However, CD is associated with dramatic changes in the gut microbiota and this was particularly evident for individuals with ileal CD.

  • 9. Erickson, Alison R
    et al.
    Cantarel, Brandi L
    Lamendella, Regina
    Darzi, Youssef
    Mongodin, Emmanuel F
    Pan, Chongle
    Shah, Manesh
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Internal Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Henrissat, Bernard
    Raes, Jeroen
    Verberkmoes, Nathan C
    Fraser, Claire M
    Hettich, Robert L
    Jansson, Janet K
    Integrated metagenomics/metaproteomics reveals human host-microbiota signatures of Crohn's disease2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 11, article id e49138Article in journal (Refereed)
    Abstract [en]

    Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.

  • 10.
    Eriksson, Carl
    et al.
    Dept Med, Div Gastroenterol, Örebro Univ Hosp, Örebro, Sweden.
    Gustavsson, Anders
    Örebro University, School of Health and Medical Sciences.
    Kronvall, Thomas
    Dept Cardiol, Örebro Univ Hosp, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Hepatotoxicity by bosentan in a patient with portopulmonary hypertension: a case-report and review of the literature2011In: Journal of Gastrointestinal and Liver Diseases, ISSN 1841-8724, E-ISSN 1842-1121, Vol. 20, no 1, p. 77-80Article in journal (Refereed)
    Abstract [en]

    Bosentan is an endothelin receptor antagonist approved for treatment of pulmonary arterial hypertension. Mild liver reactions occur in about 10% of treated patients but severe hepatotoxicity is rare. We present clinical data and treatment outcome of a severe drug induced liver injury due to bosentan in a patient with non-cirrhotic portopulmonary hypertension. After 18 months of uncomplicated therapy with bosentan 125 mg b.i.d., the patient developed a severe mixed hepatic injury. Serum levels of bilirubin were 316 µmol/l (ref. value <20 micromol/l), AST 14 µkat/l (ref. value < 0.9 µkat/l), ALT 10 µkat/l (ref. value < 0.9 µkat/l), ALP 8 µkat/l (ref. value <1.8 µkat/l) and INR 1.8 (ref. value 0.9-1.1). Complete diagnostic work-up disclosed no other cause of hepatotoxicity. Treatment with prednisolone 40 mg/day in tapering doses was ultimately added and the patient made a full recovery. Subsequent treatment with sildenafil and ambrisentan for pulmonary arterial hypertension was well tolerated and liver function tests have remained normal during 12 months' follow-up. A review of the literature revealed three other women with severe hepatotoxicity due to bosentan. Bosentan may cause severe liver injury, even after long uneventful therapy, and current recommendations on regular monitoring of liver function tests are reinforced. Ambrisentan may be a therapeutic alternative in patients with pulmonary arterial hypertension and hepatotoxicity by bosentan.

  • 11.
    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.

  • 12.
    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. University of Glasgow, Institute of Infection, College of Medical, 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. Örebro University, Division of Gastroenterology, Department of Medicine, 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.

  • 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.
    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)
  • 14.
    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)
  • 15.
    Gustavsson, A.
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Blomberg, B.
    Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, Sweden.
    Andersson, Magnus V.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Division of Gastroenterology, Department of Medicine, Örebro University Hospital, Örebro, 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.
    Letter: endoscopic balloon dilatation or strictureplasty for stricturing Crohn's disease? Authors' reply2012In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 36, no 4, p. 404-404Article in journal (Refereed)
  • 16. Gustavsson, A.
    et al.
    Järnerot, G.
    Hertervig, E.
    Friis-Liby, I.
    Blomquist, L.
    Karlen, P.
    Grännö, C.
    Vilien, M.
    Ström, M.
    Verbaan, H.
    Hellström, P. M.
    Halfvarson, Jonas
    Magnuson, A.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Colectomy after rescue therapy for intravenous-steroid resistant acute ulcerative colitis: a 3-year follow-up study of the Swedish-Danish infliximab/placebo trial2008In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 57(Suppl 1), p. A79-A79Article in journal (Refereed)
  • 17. Gustavsson, A.
    et al.
    Magnuson, A.
    Blomberg, B.
    Andersson, Magnus V.
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Endoskopisk dilatation av strikturerande Crohns sjukdom2011In: Gastrokuriren, ISSN 1651-0453, Vol. 16, no 29, p. MP-13-MP-13Article in journal (Other academic)
  • 18.
    Gustavsson, Anders
    et al.
    Örebro University, School of Health and Medical Sciences.
    Halfvarson, Jonas
    Magnuson, Anders
    Sandberg-Gertzén, Hanna
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Järnerot, Gunnar
    Long-term colectomy rate after intensive intravenous corticosteroid therapy for ulcerative colitis prior to the immunosuppressive treatment era2007In: American Journal of Gastroenterology, ISSN 0002-9270, E-ISSN 1572-0241, Vol. 102, no 11, p. 2513-2519Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Corticosteroids are a cornerstone in the treatment of a severe attack of ulcerative colitis (UC). The long-term prognosis in this patient group is not well described. We studied the long-term colectomy and relapse rates in patients given intensive intravenous corticosteroid treatment (IIVT) for acute UC. METHODS: A retrospective clinical study of 158 patients with UC treated in 1975-1982 with IIVT. Patients were followed-up to death, colectomy or last visit. RESULTS: A total of 11 patients were excluded due to change of diagnosis (N = 10) or lost to follow-up (N = 1). The indication for index IIVT in the remaining 147 patients was a severe attack (N = 61), a moderately severe attack (N = 45), a mild attack (N = 29) or chronic continuous disease (N = 12). The median (range) duration of follow-up was 173 (4-271) months in patients escaping colectomy during the first 3 months. Three months after IIVT, the colectomy rates were 28/61 (46%) in a severe attack, 4/45 (9%) in a moderately severe, and 1/29 (3%) in a mild attack. After 10 yr, the colectomy rates were 39/61 (64%), 22/45 (49%), and 8/29 (28%), respectively. During follow-up, neither colectomy incidence beyond 3 months, time to first relapse nor relapse incidence was influenced by severity of initial attack, except for a lower relapse incidence after a severe attack. CONCLUSIONS: In patients escaping colectomy during the first 3 months after IIVT, the future prognosis was similar irrespective of initial disease severity.

  • 19.
    Gustavsson, Anders
    et al.
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Järnerot, G.
    School of Health and Medical Science, Örebro University, Örebro, Sweden; Örebro University Hospital, Örebro, Sweden.
    Hertervig, E.
    Örebro University Hospital, Örebro, Sweden.
    Friis-Liby, I.
    Dept Med, Div Gastroenterol, Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Blomquist, L.
    Dept Gastroenterol & Hepatol, Karolinska Univ Hosp, Stockholm, Sweden.
    Karlén, P.
    Dept Med, Div Gastroenterol, Södersjukhuset, Stockholm, Sweden.
    Grännö, C.
    Dept Med, Div Gastroenterol, Ryhov Hosp, Jönköping, Sweden.
    Vilien, M.
    Div Gastroenterol, Hillerød Hosp, Hillerød, Denmark.
    Ström, M.
    Fac Hlth Sci, Div Gastroenterol & Hepatol, Linköping Univ, Linköping, Sweden.
    Verbaan, H.
    Dept Med, Div Gastroenterol, Malmö Gen Univ Hosp, Malmö, Sweden .
    Hellström, P. M.
    Dept Gastroenterol & Hepatol, Karolinska Univ Hosp, Stockholm, Sweden.
    Magnuson, A.
    Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences. Örebro University Hospital, Örebro, Sweden.
    Clinical trial: colectomy after rescue therapy in ulcerative colitis-3-year follow-up of the Swedish-Danish controlled infliximab study2010In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 32, no 8, p. 984-989Article in journal (Refereed)
    Abstract [en]

    Background The long-term efficacy of infliximab as rescue therapy in steroid-refractory ulcerative colitis is not well described. Aim To examine the long-term efficacy of infliximab as a rescue therapy through a 3-year follow-up of a previous placebo-controlled trial of infliximab in acute steroid-refractory ulcerative colitis. Method In the original study, 45 patients were randomized to a single infusion of infliximab 5 mg/kg or placebo, and at 3 months, 7/24 patients given infliximab were operated vs. 14/21 patients given placebo. Three years or later, patients were asked to participate in a clinical follow-up. Results Another seven patients underwent colectomy during follow-up: five in the infliximab group and two in the placebo group. After 3 years, a total of 12/24 (50%) patients given infliximab and 16/21 (76%) given placebo (P = 0.012) had a colectomy. None of eight patients in endoscopic remission at 3 months later had a colectomy compared with 7/14 (50%) patients who were not in remission (P = 0.02). There was no mortality. Conclusion The benefit of rescue therapy with infliximab in steroid-refractory acute ulcerative colitis remained after 3 years. The main advantage of infliximab treatment occurred during the first 3 months, whereas subsequent colectomy rates were similar in the two groups. Mucosal healing at 3 months influenced later risk of colectomy.

  • 20.
    Gustavsson, Anders
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Magnuson, A.
    Unit of Statistics and Epidemiology, Centre for Clinical Research, Örebro University Hospital, Örebro, Sweden.
    Blomberg, B.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Magnus V.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    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. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Endoscopic dilation is an efficacious and safe treatment of intestinal strictures in Crohn's disease2012In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 36, no 2, p. 151-158Article in journal (Refereed)
    Abstract [en]

    Background: Bowel strictures are a major cause of morbidity, hospitalisation and surgery in Crohn's disease.

    Aim: We report short- and long-term efficacy and safety of endoscopic balloon dilation of strictures due to Crohn's disease.

    Methods: Retrospective study of patients who underwent endoscopic balloon dilation between 1987 and 2009.

    Results: We performed 776 dilations, of which 621 (80%) were on anastomotic strictures, in 178 patients (94 women) with Crohn's disease. At first dilation, median (IQR) age of patients was 45 (37-56) years and disease duration 16 (8-22) years. Technical success rate was 689/776 (89%). A subset of 75 patients from the primary catchment area, with >5-year follow-up, underwent a total of 246 dilations. At 1-year follow-up, 60/75 (80%) patients had undergone no further intervention or one additional dilation only. At 3 and 5 years, corresponding figures were 43/75 (57%) and 39/75 (52%). Cumulative proportions of patients undergoing surgery at 1, 3 and 5 years were 13%, 28% and 36%. Complication rate per procedure for all 178 patients was 41/776 (5.3%), bowel perforation (n = 11, 1.4%), major bleeding requiring blood transfusion (n = 8, 1.0%), minor bleeding (n = 10, 1.3%) and abdominal pain or fever (n = 12, 1.5%). Ten patients underwent surgery due to complications (perforation n = 8, bleeding n = 2). There was no procedure-related mortality.

    Conclusion: Endoscopic balloon dilation is an efficacious and safe alternative to surgical resection of intestinal strictures in Crohn's disease. At 5-year follow-up, 52% of patients required no further or one additional dilation only, whereas 36% had undergone surgical resection. Complication frequency was low.

  • 21.
    Gustavsson, Anders
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden; Department of Internal Medicine, Karlstad Hospital, Karlstad, Sweden.
    Magnuson, A.
    Clinical Epidemiology and Biostatistics Unit, Örebro University Hospital, Örebro, Sweden.
    Blomberg, B.
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Magnus V.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Örebro, Sweden.
    Letter: the impact of smoking on clinical outcomes after endoscopic dilatation in Crohn's disease - authors' reply2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 4, p. 500-501Article in journal (Refereed)
  • 22. Gustavsson, Anders
    et al.
    Magnuson, Anders
    Blomberg, Björn
    Andersson, Magnus V.
    Halfvarson, Jonas
    Örebro University, School of Medicine, Örebro University, Sweden.
    Tysk, Curt
    Endoscopic Balloon Dilation of Intestinal Strictures in Crohn's Disease2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 140, no 5, p. S140-S140Article in journal (Other academic)
  • 23.
    Gustavsson, Anders
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Magnuson, Anders
    Clinical Epidemiology and Biostatistics Unit, Örebro University Hospital, Örebro, Sweden.
    Blomberg, Björn
    Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Magnus V.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Halfvarson, Jonas
    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.
    Smoking is a risk factor for recurrence of intestinal stricture after endoscopic dilation in Crohn's disease2013In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 37, no 4, p. 430-437Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Endoscopic balloon dilation is an efficacious and safe alternative to surgery as treatment of short intestinal strictures in Crohn's disease (CD). Factors predicting outcome of the procedure are not well described.

    AIM: To evaluate whether smoking at diagnosis, treatment with azathioprine, or other clinical variables may affect clinical outcome after endoscopic dilation. The endpoint was requirement of a new intervention such as dilation or surgery with intestinal resection or strictureplasty.

    METHODS: Retrospective study of 83 patients with CD who underwent endoscopic balloon dilation of an intestinal stricture between 1987 and 2009.

    RESULTS: After index dilation 55/83 patients underwent a new intervention. Among current smokers, 31/32 (97%) underwent another intervention compared to 18/33 (55%) among never smokers (adjusted HR: 2.50, 95% CI: 1.14-5.50, P = 0.022). After 5 years, cumulative probability of new intervention was 0.81 in smokers compared to 0.52 in never smokers; difference 0.29 (95% CI: 0.07-0.52, P = 0.01). In 16 patients, therapy with azathioprine was initiated before or shortly after the index dilation; 7/16 underwent a new intervention compared to 48/67 of those without azathioprine (HR: 0.46, 95% CI: 0.21-1.03, P = 0.06). After adjustment for other variables, the association was even weaker (HR: 0.80, 95% CI: 0.29-2.18, P = 0.668). Sex, age at diagnosis, age at first dilation, balloon size, location of stricture, and treatment period did not influence outcome.

    CONCLUSIONS: Smoking doubles the risk of recurrent stricture formation requiring a new intervention after index dilation. Maintenance therapy with azathioprine did not influence the subsequent course and need for a new intervention.

  • 24. 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)
  • 25. 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)
  • 26.
    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, Sweden.
    Eriksson, S.
    Department of Pathology, Örebro University Hospital, Örebro, Örebro, Sweden.
    Bohr, Johan
    School of Health and Medical Sciences, Örebro University, Sweden; Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Region Örebro County, Sweden.
    Nyhlin, Nils
    Örebro University Hospital. Department of Medicine, Division of Gastroenterology.
    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).

  • 27.
    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.

  • 28. Halfvarson, Jonas
    et al.
    Dicksved, J.
    Rosenquist, M.
    Willing, E.
    Järnerot, G.
    Engstrand, L.
    Jansson, J. K.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Bakteriefloran hos tvillingar med Crohns sjukdom2008In: Gastrokuriren, Vol. 13, no 29 PO-08Article in journal (Other academic)
  • 29. Halfvarson, Jonas
    et al.
    Dicksved, Johan
    Rosenquist, Magnus
    Järnerot, Gunnar
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Engstrand, Lars
    Jansson, Janet K.
    W1182 molecular fingerprinting of the gut microbiota of twins reveals differences according to Crohn's disease2008In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 134, no 4, Supplement 1, p. A-650-A-650Article in journal (Refereed)
  • 30.
    Halfvarson, Jonas
    et al.
    Örebro University, School of Medicine, Örebro University, Sweden.
    Jess, Tine
    Bodin, Lennart
    Örebro University, Örebro University School of Business.
    Järnerot, Gunnar
    Munkholm, Pia
    Binder, Vibeke
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Longitudinal concordance for clinical characteristics in a Swedish-Danish twin population with inflammatory bowel disease2007In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 13, no 12, p. 1536-1544Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The genetic influence on disease course in inflammatory bowel disease (IBD) remains unknown. We therefore aimed to study longitudinal concordance for clinical characteristics and longitudinal stability using the Montreal Classification in an IBD twin population. METHODS: A total of 158 twins with ulcerative colitis (UC) (18 belonging to 9 concordant monozygotic pairs) and 141 twins with Crohn's disease (CD) (34 belonging to 17 concordant monozygotic pairs) were enrolled. Medical notes were scrutinized for clinical characteristics at diagnosis and after 10 years. Using the binominal distribution, we tested the hypothesis that clinical characteristics were independent within individuals in disease concordant monozygotic pairs. RESULTS: In CD, location was identical in 11/17 monozygotic concordant pairs at diagnosis (P = 0.008) and in 11/16 pairs after 10 years (P = 0.02). Behavior at diagnosis was identical in 13/17 pairs (P = 0.03) and in 11/16 pairs after 10 years (P = 0.01). Monozygotic UC twins were concordant (within 5 years) for age at diagnosis (6/9 pairs; P < 0.001) and symptomatic onset (4/9 pairs; P = 0.02) but not for extent of disease at diagnosis or after 10 years. The Montreal Classification did not demonstrate longitudinal stability, either regarding location or behavior of CD or extent of UC. CONCLUSIONS: The high phenotypic concordance, both at diagnosis and longitudinally, in monozygotic twins with CD supports a genetic influence not only on disease occurrence but also on disease course. This contrasts with UC, where the genetic impact appears less. Montreal Classification characteristics changed over time and should be used cautiously.

  • 31. Halfvarson, Jonas
    et al.
    Jess, Tine
    Magnuson, Anders
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Orholm, Marianne
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Binder, Vibeke
    Järnerot, Gunnar
    Environmental factors in inflammatory bowel disease: a co-twin control study of a Swedish-Danish twin population2006In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 12, no 10, p. 925-933Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Genetics and environmental factors are implicated in the etiology of inflammatory bowel disease (IBD). We studied environmental factors in a population-based Swedish-Danish twin cohort using the co-twin control method.

    SUBJECTS AND METHODS:

    A questionnaire was sent to 317 twin pairs regarding markers of exposures in the following areas: infections/colonization and diet as well as smoking, appendectomy, and oral contraceptives. Odds ratios (OR) were calculated by conditional logistic regression. When confounding appeared plausible, multivariate conditional logistic regression was added. The questions were also divided into topic groups, and adjustment was made for multiple testing within each of the groups.

    RESULTS:

    The response rate to the questionnaire was 83%. In consideration of the study design, only discordant pairs were included (Crohn's disease [CD], n = 102; ulcerative colitis [UC], n = 125). Recurrent gastrointestinal infections were associated with both UC (OR, 8.0; 95% confidence interval [CI], 1.0-64) and CD (OR, 5.5; 95% CI, 1.2-25). Hospitalization for gastrointestinal infections was associated with CD (OR, 12; 95% CI, 1.6-92). Smoking was inversely associated with UC (OR, 0.4; 95% CI, 0.2-0.9) and associated with CD (OR, 2.9; 95% CI, 1.2-7.1).

    CONCLUSIONS:

    The observed associations indicate that markers of possible infectious events may influence the risk of IBD. Some of these effects might be mediated by long-term changes in gut flora or alterations in reactivity to the flora. The influence of smoking in IBD was confirmed.

  • 32. Hjortswang, Henrik
    et al.
    Järnerot, Gunnar
    Curman, Bengt
    Sandberg-Gertzén, Hanna
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Blomberg, Björn
    Almer, Sven
    Ström, Magnus
    The Short Health Scale: a valid measure of subjective health in ulcerative colitis2006In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 41, no 10, p. 1196-1203Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Assessment of health-related quality of life (HRQOL) is important in both clinical practice and clinical trials, and several multi-item questionnaires are currently in use. We have devised and evaluated a simplified four-item questionnaire, the Short Health Scale (SHS), representing each of four health dimensions: (a) symptom burden, (b) social function, (c) disease-related worry and (d) general well-being. MATERIAL AND METHODS: Three hundred patients with ulcerative colitis completed the SHS and three other HRQOL questionnaires (IBDQ, RFIPC and PGWB). Half of the patients repeated the questionnaires after 6 months - or earlier if disease activity changed. Test-retest reliability was derived from measurements of the SHS questions, 2 weeks apart, on 18 patients in remission. RESULTS: Patients in relapse scored higher on each of the four SHS questions than patients in remission (p < 0.001). Each of the four SHS scores were associated with results of their corresponding health dimension obtained with the other three questionnaires (rs=0.57-0.78, p < 0.001) (validity). The results of the SHS proved stable on repeated measurement with a 2-week interval in patients in remission (rs=0.71-0.91, p < 0.01) (test-retest reliability). Patients with a change in disease activity had a significant change in their SHS scores (p < 0.05) (responsiveness). CONCLUSIONS: The SHS is a valid, reliable and responsive measure of subjective health in patients with ulcerative colitis. It is simple to administer, quickly completed and the results do not need further calculations. The SHS can be used in clinical trials and in clinical practice to identify the patient's main problems affecting health.

  • 33. 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.

  • 34. 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.

  • 35. Jansson, J. K.
    et al.
    Willing, B.
    Dicksved, J.
    Halfvarson, Jonas
    Andersson, A.
    Rosenquist, M.
    Järnerot, G.
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Engstrand, L.
    Molecular fingerprinting of twins with Crohn's disease reveals the importance of dysbiosis of the gut microbiota2008Conference paper (Other academic)
  • 36. Jansson, Janet
    et al.
    Willing, Ben
    Lucio, Marianna
    Fekete, Ages
    Dicksved, Johan
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Schmitt-Kopplin, Philippe
    Metabolomics reveals metabolic biomarkers of Crohn's disease2009In: PloS one, ISSN 1932-6203, Vol. 4, no 7, p. e6386-Article in journal (Refereed)
    Abstract [en]

    The causes and etiology of Crohn's disease (CD) are currently unknown although both host genetics and environmental factors play a role. Here we used non-targeted metabolic profiling to determine the contribution of metabolites produced by the gut microbiota towards disease status of the host. Ion Cyclotron Resonance Fourier Transform Mass Spectrometry (ICR-FT/MS) was used to discern the masses of thousands of metabolites in fecal samples collected from 17 identical twin pairs, including healthy individuals and those with CD. Pathways with differentiating metabolites included those involved in the metabolism and or synthesis of amino acids, fatty acids, bile acids and arachidonic acid. Several metabolites were positively or negatively correlated to the disease phenotype and to specific microbes previously characterized in the same samples. Our data reveal novel differentiating metabolites for CD that may provide diagnostic biomarkers and/or monitoring tools as well as insight into potential targets for disease therapy and prevention.

  • 37. Järnerot, G.
    et al.
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, Department of Clinical Medicine.
    Twin studies in inflammatory bowel disease: a review2007In: Austral - Asian Journal of Cancer, ISSN 0972-2556, Vol. 6, no 1, p. 29-33Article in journal (Other academic)
  • 38. Kaminsky, Zachary A.
    et al.
    Tang, Thomas
    Wang, Sun-Chong
    Ptak, Carolyn
    Oh, Gabriel H. T.
    Wong, Albert H. C.
    Feldcamp, Laura A.
    Virtanen, Carl
    Halfvarson, Jonas
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    McRae, Allan F.
    Visscher, Peter M.
    Montgomery, Grant W.
    Gottesman, Irving I.
    Martin, Nicholas G.
    Petronis, Art
    DNA methylation profiles in monozygotic and dizygotic twins2009In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 41, no 2, p. 240-245Article in journal (Refereed)
    Abstract [en]

    Twin studies have provided the basis for genetic and epidemiological studies in human complex traits. As epigenetic factors can contribute to phenotypic outcomes, we conducted a DNA methylation analysis in white blood cells (WBC), buccal epithelial cells and gut biopsies of 114 monozygotic (MZ) twins as well as WBC and buccal epithelial cells of 80 dizygotic (DZ) twins using 12K CpG island microarrays. Here we provide the first annotation of epigenetic metastability of approximately 6,000 unique genomic regions in MZ twins. An intraclass correlation (ICC)-based comparison of matched MZ and DZ twins showed significantly higher epigenetic difference in buccal cells of DZ co-twins (P = 1.2 x 10(-294)). Although such higher epigenetic discordance in DZ twins can result from DNA sequence differences, our in silico SNP analyses and animal studies favor the hypothesis that it is due to epigenomic differences in the zygotes, suggesting that molecular mechanisms of heritability may not be limited to DNA sequence differences.

  • 39.
    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)
  • 40.
    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.

  • 41.
    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.

  • 42.
    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.

  • 43. 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)
  • 44. 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)
  • 45. 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)
  • 46.
    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.
    Bohr, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept. of Medicine, Division of Gastroenterology.
    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.

  • 47.
    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.

  • 48.
    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.

  • 49.
    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)
  • 50. Ljung, Tryggve
    et al.
    Thomsen, Ole Østergaard
    Vatn, Morten
    Karlén, Per
    Karlsen, Lars Norman
    Tysk, Curt
    Örebro University, School of Health and Medical Sciences.
    Nilsson, Stefan U.
    Kilander, Anders
    Gillberg, Rolf
    Grip, Olof
    Lindgren, Stefan
    Befrits, Ragnar
    Löfberg, Robert
    Granulocyte, monocyte/macrophage apheresis for inflammatory bowel disease: the first 100 patients treated in Scandinavia2007In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 42, no 2, p. 221-227Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Selective leukocyte apheresis is a new type of non-pharmacological treatment for patients with active ulcerative colitis and Crohn's disease. Preliminary data have indicated that this type of therapy is safe and efficacious, and large sham-controlled studies are currently in progress. In Scandinavia, a substantial number of patients with chronic inflammatory bowel disease have already received leukocyte apheresis on a compassionate use basis and the aim of this study was to report the clinical outcome and adverse events in the first patients treated. MATERIAL AND METHODS: Clinical details of the first consecutive 100 patients with inflammatory bowel disease treated with granulocyte, monocyte/macrophage (Adacolumn) apheresis in Scandinavia were prospectively registered. Median length of follow-up was 17 months, (range 5-30). RESULTS: The study population comprised 52 patients with ulcerative colitis, 44 patients with Crohn's disease and 4 patients with indeterminate colitis. In 97 patients the indication for Adacolumn treatment was steroid-refractory or steroid-dependent disease. Clinical remission was attained in 48% of the patients with ulcerative colitis, and an additional 27% had a clinical response to the apheresis treatment. The corresponding figures for patients with Crohn's disease were 41% and 23%, respectively. Complete steroid withdrawal was achieved in 27 out of the 50 patients taking corticosteroids at baseline. Adverse events were reported in 15 patients and headache was most frequently reported (n=7). CONCLUSIONS: Granulocyte, monocyte/macrophage apheresis treatment seems to be a valuable adjuvant therapy in selected patients with refractory inflammatory bowel disease. The risk for toxicity or severe adverse events appears to be low.

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