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Giannakopoulos, G., Verbaan, H., Friis-Liby, I.-L., Sangfelt, P., Nyhlin, N. & Almer, S. (2019). Mycophenolate mofetil treatment in patients with autoimmune hepatitis failing standard therapy with prednisolone and azathioprine. Digestive and Liver Disease, 51(2), 253-257
Open this publication in new window or tab >>Mycophenolate mofetil treatment in patients with autoimmune hepatitis failing standard therapy with prednisolone and azathioprine
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2019 (English)In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 51, no 2, p. 253-257Article in journal (Refereed) Published
Abstract [en]

Background: Data on rescue treatment of autoimmune hepatitis in patients that fail standard treatment are sparse.

Aims: To report our long-term experience with mycophenolate mofetil.

Methods: Retrospective study in 22 patients with autoimmune hepatitis who failed azathioprine and prednisolone due to adverse events (n = 14, 64%), lack of remission (n = 5, 23%) or a combination (n=3, 13%).

Results: Mycophenolate mofetil was started at a dose of 20 mg/kg/day and increased to a maximum of 3 g/day. Follow-up was 0-6 months in 7 patients; more than 12 months in 15 (68%) and more than 24 months in 10. Normal aminotransferase levels were obtained (n = 3) or maintained (n = 7) in 10 patients (45%) after three to 30 weeks. 12 patients (55%) were withdrawn during the first 6 months, due to adverse events. Three patients were switched to cyclosporine and one underwent liver transplantation. Successful treatment with mycophenolate mofetil continued in 10 patients (45%) for a median of 71 months (range 20-124). Of these, one stopped prednisolone, five have a prednisolone dose <5 mg daily and four patients 5-10 mg.

Conclusion: Approximately one of two patients with autoimmune hepatitis that fail standard treatment benefit from long-term maintenance with mycophenolate mofetil, especially those with previous intolerance to thiopurines, where mycophenolate mofetil is effective in two thirds. (C) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Autoimmune hepatitis, Mycophenolate mofetil, Thiopurine failure
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-72428 (URN)10.1016/j.dld.2018.10.004 (DOI)000457115900011 ()30389427 (PubMedID)2-s2.0-85055677387 (Scopus ID)
Note

Funding Agency:

Meda AB, Sweden

Available from: 2019-02-14 Created: 2019-02-14 Last updated: 2019-02-14Bibliographically approved
Eriksson, C., Henriksson, I., Brus, O., Zhulina, Y., Nyhlin, N., Tysk, C., . . . Halfvarson, J. (2018). Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease: a population-based cohort study. Alimentary Pharmacology and Therapeutics, 48(6), 638-645
Open this publication in new window or tab >>Incidence, prevalence and clinical outcome of anaemia in inflammatory bowel disease: a population-based cohort study
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2018 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 48, no 6, p. 638-645Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The incidence and short-term outcome of anaemia in inflammatory bowel disease (IBD) are largely unknown.

AIM: To determine the incidence, prevalence and clinical outcome of anaemia in terms of resolution of anaemia within 12 months. We also planned to assess risk factors for anaemia in IBD.

METHODS: A random sample of 342 patients was obtained from the population-based IBD cohort of Örebro University Hospital, Sweden, consisting of 1405 patients diagnosed between 1963 and 2010. Haemoglobin measurements recorded from 1 January 2011 to 31 December 2013 were extracted from the Clinical Chemistry data system.

RESULTS: In Crohn's disease, the incidence rate of anaemia was 19.3 (95% CI: 15.4-23.7) per 100 person-years and the prevalence was 28.7% (CI: 22.0-36.2), compared with 12.9 (CI: 9.8-16.5) and 16.5% (CI: 11.2-22.9) for ulcerative colitis. Crohn's disease was associated with an increased incidence (OR = 1.60; CI: 1.02-2.51) and prevalence of anaemia (OR = 2.04; CI: 1.20-3.46) compared to ulcerative colitis. Stricturing disease phenotype in Crohn's disease (HR = 2.59; CI: 1.00-6.79) and extensive disease in ulcerative colitis (HR = 2.40; CI: 1.10-5.36) were associated with an increased risk of anaemia. Despite a higher probability of receiving specific therapy within 3 months from the diagnosis of anaemia, Crohn's disease patients had a worse outcome in terms of resolution of anaemia within 12 months (56% vs 75%; P = 0.03).

CONCLUSIONS: Anaemia is a common manifestation of IBD even beyond the first years after the diagnosis of IBD. Crohn's disease is associated with both an increased risk and a worse outcome.

Place, publisher, year, edition, pages
Blackwell Science Ltd., 2018
National Category
Gastroenterology and Hepatology General Practice
Identifiers
urn:nbn:se:oru:diva-68681 (URN)10.1111/apt.14920 (DOI)000442338900006 ()30069892 (PubMedID)2-s2.0-85051863489 (Scopus ID)
Note

Funding agency:

Swedish government's Agreement on Medical Training and Research

Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2018-09-06Bibliographically approved
Wickbom, A., Bohr, J., Nyhlin, N., Eriksson, A., Lapidus, A., Münch, A., . . . Tysk, C. (2018). Microscopic colitis in patients with ulcerative colitis or Crohn's disease: a retrospective observational study and review of the literature. Scandinavian Journal of Gastroenterology, 53(4), 410-416
Open this publication in new window or tab >>Microscopic colitis in patients with ulcerative colitis or Crohn's disease: a retrospective observational study and review of the literature
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2018 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 53, no 4, p. 410-416Article, review/survey (Refereed) Published
Abstract [en]

OBJECTIVES: Onset of microscopic colitis (MC) in patients with ulcerative colitis (UC) or Crohn's disease (CD), or vice versa, has been reported occasionally but the subject is not well described. We therefore report a retrospective observational study of such patients and review the literature.

METHODS: Forty-six Swedish gastroenterology clinics were contacted about patients with diagnoses of both inflammatory bowel disease (IBD) and MC. Publications were searched on PubMed.

RESULTS: We identified 31 patients with onset of MC after a median (range) of 20 (2-52) years after diagnosis of IBD, or vice versa; 21 UC patients developed collagenous colitis (CC) (n = 16) or lymphocytic colitis (LC) (n = 5); nine CD patients developed CC (n = 5) or LC (n = 4); one CC patient developed CD. Of the 21 UC patients, 18 had extensive disease, whereas no consistent phenotype occurred in CD. Literature review revealed 27 comprehensive case reports of patients with diagnoses of both IBD and MC. Thirteen MC patients developed IBD, of which four required colectomy. Fourteen IBD patients later developed MC. There were incomplete clinical data in 115 additional reported patients.

CONCLUSIONS: Altogether 173 patients with occurrence of both IBD and MC were found. The most common finding in our patients was onset of CC in a patient with UC. Although these are likely random associations of two different disorders, MC should be considered in the patient with UC or CD if there is onset of chronic watery diarrhoea without endoscopic relapse of IBD.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018
Keywords
Collagenous colitis; lymphocytic colitis; microscopic colitis; ulcerative colitis; Crohn's disease; inflammatory bowel disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-65940 (URN)10.1080/00365521.2018.1430252 (DOI)000430726600005 ()29546806 (PubMedID)2-s2.0-85044046582 (Scopus ID)
Note

Funding Agency:

Örebro County Research Committee

Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2018-09-04Bibliographically approved
Borssen, Å. D., Marschall, H.-U., Bergquist, A., Rorsman, F., Weiland, O., Kechagias, S., . . . Werner, M. (2017). Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis. Scandinavian Journal of Gastroenterology, 52(9), 1022-1028
Open this publication in new window or tab >>Epidemiology and causes of death in a Swedish cohort of patients with autoimmune hepatitis
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2017 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 52, no 9, p. 1022-1028Article in journal (Refereed) Published
Abstract [en]

Background: Epidemiological studies of autoimmune hepatitis (AIH) show varying figures on prevalence and incidence, and data on the long-term prognosis are scarce.

Objective: To investigate the epidemiology, long-term prognosis and causes of death in a Swedish AIH cohort.

Material and methods: Data collected from 634 AIH patients were matched to the Cause of Death Registry, and survival analyses were made. Prevalence and incidence were calculated for university hospitals with full coverage of cases and compared to the County of Vasterbotten in Northern Sweden.

Results: AIH point prevalence was 17.3/100,000 inhabitants in 2009, and the yearly incidence 1990-2009 was 1.2/100,000 inhabitants and year. The time between diagnosis and end of follow-up, liver transplantation or death was in median 11.3 years (range 0-51.5 years). Men were diagnosed earlier (p<.001) and died younger than women (p=.002). No gender differences were found concerning transplant-free, overall survival and liver-related death. Cirrhosis at diagnosis was linked to an inferior survival (p<.001). Liver-related death was the most common cause of death (32.7%). The relative survival started to diverge from the general population 4 years after diagnosis but a distinct decline was not observed until after more than 10 years.

Conclusions: Long-term survival was reduced in patients with AIH. No gender difference regarding prognosis was seen but men died younger, probably as a result of earlier onset of disease. Cirrhosis at diagnosis was a risk factor for poor prognosis and the overall risk of liver-related death was increased.

Place, publisher, year, edition, pages
Taylor & Francis, 2017
Keywords
Autoimmune hepatitis, epidemiology, causes of death, liver, cirrhosis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-58978 (URN)10.1080/00365521.2017.1335772 (DOI)000404368000016 ()28562110 (PubMedID)2-s2.0-85020075816 (Scopus ID)
Note

Funding Agencies:

Bengt Ihre fund  

Meda 

Available from: 2017-08-01 Created: 2017-08-01 Last updated: 2017-10-23Bibliographically approved
Wickbom, A., Nyhlin, N., Montgomery, S. M., Bohr, J. & Tysk, C. (2017). Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study. European Journal of Gastroenterology and Hepathology, 29(5), 587-594
Open this publication in new window or tab >>Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study
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2017 (English)In: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 29, no 5, p. 587-594Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: Data on heredity, risk factors and comorbidity in microscopic colitis, encompassing collagenous colitis (CC) and lymphocytic colitis (LC), are limited.

AIM: The aim was to carry out a case-control study of family history, childhood circumstances, educational level, marital status, smoking and comorbidity in microscopic colitis.

METHODS: A postal questionnaire was sent in 2008-2009 to microscopic colitis patients resident in Sweden and three population-based controls per patient, matched for age, sex and municipality.

RESULTS: Some 212 patients and 627 controls participated in the study. There was an association with a family history of microscopic colitis in both CC [odds ratio (OR): 10.3; 95% confidence interval (CI): 2.1-50.4, P=0.004] and LC (OR not estimated, P=0.008). Current smoking was associated with CC [OR: 4.7; 95% CI: 2.4-9.2, P<0.001) and LC (OR: 3.2; 95% CI: 1.6-6.7, P=0.002). The median age at diagnosis was around 10 years earlier in ever-smokers compared with never-smokers.CC was associated with a history of ulcerative colitis (UC) (OR: 8.7, 95% CI: 2.2-33.7, P=0.002), thyroid disease (OR: 2.3; 95% CI: 1.1-4.5, P=0.02), coeliac disease (OR: 13.1; 95% CI: 2.7-62.7, P=0.001), rheumatic disease (OR 1.9; 95% CI: 1.0-3.5, P=0.042) and previous appendicectomy (OR: 2.2; 95% CI: 1.3-3.8, P=0.003), and LC with UC (OR: 6.8; 95% CI: 1.7-28.0, P=0.008), thyroid disease (OR: 2.4; 95% CI: 1.1-5.4, P=0.037) and coeliac disease (OR: 8.7; 95% CI: 2.8-26.7, P<0.001).

CONCLUSION: Association with a family history of microscopic colitis indicates that familial factors may be important. The association with a history of UC should be studied further as it may present new insights into the pathogenesis of microscopic colitis and UC.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
Keywords
inflammatory bowel diseases; microscopic colitis; risk factors; smoking
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-57572 (URN)10.1097/MEG.0000000000000832 (DOI)000398812100015 ()28350750 (PubMedID)2-s2.0-85016730155 (Scopus ID)
Funder
Swedish Society of Medicine
Note

Other funding Agencies:

Örebro University Hospital Research Foundation (Nyckelfonden)

Bengt Ihre Foundation  22100-2009  98031-2010  176271-2011

Örebro County Research Committee

Available from: 2017-05-04 Created: 2017-05-04 Last updated: 2018-07-20Bibliographically approved
Borssén, Å. D., Palmqvist, R., Kechagias, S., Marschall, H.-U., Bergquist, A., Rorsman, F., . . . Werner, M. (2017). Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study. Medicine (Baltimore, Md.), 96(34), Article ID e7708.
Open this publication in new window or tab >>Histological improvement of liver fibrosis in well-treated patients with autoimmune hepatitis: A cohort study
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2017 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 96, no 34, article id e7708Article in journal (Refereed) Published
Abstract [en]

Autoimmune hepatitis (AIH) is a chronic autoimmune liver disease that if left untreated may lead to the development of cirrhosis. Previous studies on AIH patients have suggested that fibrosis and even cirrhosis can be reversed by medical treatment. The aim of this study was to evaluate the efficacy of medical treatment for protection of developing fibrosis and cirrhosis.

A total of 258 liver biopsies from 101 patients (72 women, 29 men) were analyzed by a single pathologist and classified according to the Ishak grading (inflammation) and staging (fibrosis) system. Liver histology was stratified according to the temporal changes of fibrosis stage (increased, decreased, or stable), and groups were compared.

Complete or partial response to medical treatment was 94.9%. Reduction of fibrosis stage from the first to the last biopsy was seen in 63 patients (62.4%). We found an association between a reduction in the fibrosis stage and continuous glucocorticoid medication, as well as lowered scores of inflammation at last biopsy. Twenty-one patients had cirrhosis (Ishak stage 6) at least in one of the previous biopsies, but only 5 patients at the last biopsy.

Histological improvement is common in AIH patients that respond to medical treatment, and a reduction or stabilization of fibrosis stage occurs in about 2/3 of such patients.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
Keywords
autoimmune hepatitis, autoimmune liver disease, cirrhosis, fibrosis, inflammation
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-61042 (URN)10.1097/MD.0000000000007708 (DOI)000408504800012 ()28834875 (PubMedID)2-s2.0-85028690293 (Scopus ID)
Note

Funding Agencies:

Albireo, Gothenburg, Sweden  

Intercept, San Diego, CA, USA  

Bengt Ihre's fund  

Västerbotten County, Umeå University Hospital 

Available from: 2017-09-19 Created: 2017-09-19 Last updated: 2018-08-31Bibliographically approved
Gunaltay, S., Repsilber, D., Helenius, G., Nyhlin, N., Bohr, J., Hultgren, O. & Hultgren Hörnquist, E. (2017). Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis. Inflammatory Bowel Diseases, 23(6), 932-945
Open this publication in new window or tab >>Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
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2017 (English)In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, no 6, p. 932-945Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2017
Keywords
collagenous colitis, lymphocytic colitis, next-generation sequencing, ulcerative colitis, T-cell repertoire analysis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-59319 (URN)10.1097/MIB.0000000000001127 (DOI)000405609200014 ()28498152 (PubMedID)2-s2.0-85019705487 (Scopus ID)
Note

Funding Agencies:

Swedish Society of Medicine (Bengt Ihre Foundation)  SLS-176271/2011  98031/2010 

Örebro University Hospital Research Foundation (Nyckelfonden)  

Research Committee, Örebro County Council  

Örebro University 

Available from: 2017-08-25 Created: 2017-08-25 Last updated: 2018-09-04Bibliographically approved
Amcoff, K., Joossens, M., Pierik, M. J., Jonkers, D., Bohr, J., Joossens, S., . . . Halfvarson, J. (2016). Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease. Journal of Crohn's & Colitis, 10(6), 695-702
Open this publication in new window or tab >>Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease
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2016 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 6, p. 695-702Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Oxford University Press, 2016
Keywords
Crohn’s disease, serology, genetics
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:oru:diva-50589 (URN)10.1093/ecco-jcc/jjw021 (DOI)000377920100010 ()26818662 (PubMedID)
Available from: 2016-06-08 Created: 2016-06-08 Last updated: 2018-07-13Bibliographically approved
Gunaltay, S., Kumawat, A. K., Nyhlin, N., Bohr, J., Tysk, C., Hultgren, O. & Hultgren-Hörnquist, E. (2015). Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment. Mediators of Inflammation, Article ID 132458.
Open this publication in new window or tab >>Enhanced levels of chemokines and their receptors in the colon of microscopic colitis patients indicate mixed immune cell recruitment
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2015 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 132458Article in journal (Refereed) Published
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.

National Category
Cell and Molecular Biology Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:oru:diva-44605 (URN)10.1155/2015/132458 (DOI)000353128700001 ()2-s2.0-84928473938 (Scopus ID)
Note

Funding Agencies:

Örebro University Hospital Research Foundation (Nyckelfonden)

Research Committee, Orebro County Council

Örebro University

Available from: 2015-05-12 Created: 2015-05-12 Last updated: 2018-06-30Bibliographically approved
Kumawat, A. K., Nyhlin, N., Wickbom, A., Tysk, C., Bohr, J., Hultgren, O. & Hultgren-Hörnquist, E. (2014). 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 Cells. Mediators of Inflammation, Article ID 879843.
Open this publication in new window or tab >>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 Cells
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2014 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, article id 879843Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
New York, USA: Hindawi Publishing Corporation, 2014
National Category
Cell and Molecular Biology Immunology in the medical area
Research subject
Immunology; Cell Research
Identifiers
urn:nbn:se:oru:diva-39815 (URN)10.1155/2014/879843 (DOI)000344673500001 ()25332518 (PubMedID)2-s2.0-84912000717 (Scopus ID)
Note

Funding Agencies:

Swedish Society of Medicine (Bengt Ihre Foundation) SLS-176271/2011  98031/2010

Nyckelfonden at Örebro University Hospital

Örebro University Hospital Research Foundation

Lars Hierta Foundation

Available from: 2014-12-16 Created: 2014-12-16 Last updated: 2019-03-26Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-0942-0816

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