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Lushnikova, A., Sjöberg, K., Münch, A., Lange, A., Bohr, J., Hultgren, O. & Hultgren Hörnquist, E. (2021). Altered levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls. Paper presented at 6th Annual International Remote Conference, Science & Society, (Online conference), February 20-21, 27, 2021. Journal of Immunology, 206(Suppl.), Article ID 17.09.
Öppna denna publikation i ny flik eller fönster >>Altered levels of immune checkpoint molecules in colon biopsies and sera from microscopic colitis and ulcerative colitis patients compared to controls
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2021 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 206, nr Suppl., artikel-id 17.09Artikel i tidskrift, Meeting abstract (Övrigt vetenskapligt) Published
Abstract [en]

Background: Microscopic colitis (MC), comprising lymphocytic colitis (LC) and collagenous colitis (CC), is an inflammatory bowel disorder. MC patients have a lower risk of developing colorectal cancer (CRC) than ulcerative colitis (UC) patients. We hypothesize that the immune response in MC is geared more towards immune surveillance of tumor cells than that of UC, which instead contributes to inflammation-associated CRC.

Methods: Using Luminex, protein levels of 14 immune checkpoints (TIM-3, CD28, CD137, CD27, CD152, HVEM, IDO, LAG-3, BTLA, GITR, CD80, PD-1, PD-L1, PD-L2) in protein lysates from colon biopsies (controls, n = 9; diarrhea controls, n = 7; LC, n = 14; CC, n = 15; UC, n = 17) were analyzed. Soluble checkpoints were analyzed in serum (23 controls, 17 LC, 36 CC and 2 UC).

Results: In patients with active LC and CC, CD137, IDO, and CD80 levels were increased compared with one or both control groups. CD152 and PD-1 levels were increased in patients with active CC compared with both control groups. In patients with active UC, levels of CD137, CD152, BTLA, PD-1, and PD-L2 were increased compared with both control groups, IDO levels were increased compared with controls, and CD80 levels were raised compared with diarrhea controls.

In sera, CD27, IDO, CD80, PD-1, and PD-L2 levels were decreased in LC patients compared to controls.

Conclusions: Increased levels of immune checkpoint molecules in colon biopsies from UC and MC patients are likely a sign of inflammation and may indicate what kind of homeostatic feed-back mechanisms are active to balance inflammation. Lowered concentrations of soluble immune checkpoint molecules in sera from patients with LC indicate a different level of homeostatic balance systemically in LC patients versus controls.

Ort, förlag, år, upplaga, sidor
American Association of Immunologists, 2021
Nationell ämneskategori
Immunologi inom det medicinska området
Identifikatorer
urn:nbn:se:oru:diva-95709 (URN)000713665800133 ()
Konferens
6th Annual International Remote Conference, Science & Society, (Online conference), February 20-21, 27, 2021
Tillgänglig från: 2021-12-03 Skapad: 2021-12-03 Senast uppdaterad: 2021-12-03Bibliografiskt granskad
Münch, A., Mihaly, E., Nagy, F., Madisch, A., Kupcinskas, J., Miehlke, S., . . . Munck, L. K. (2021). Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial. United European Gastroenterology journal, 9(7), 837-847
Öppna denna publikation i ny flik eller fönster >>Budesonide as induction therapy for incomplete microscopic colitis: A randomised, placebo-controlled multicentre trial
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2021 (Engelska)Ingår i: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 9, nr 7, s. 837-847Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background and aims: Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi.

Methods: Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of <3 stools/day and a mean of <1 watery stool/day in the 7 days before week 8.

Results: Due to insufficient patient recruitment, the trial was discontinued prematurely. The intention-to-treat analysis included 44 patients (21 budesonide and 23 placebo). The primary endpoint of clinical remission at week 8 was obtained by 71.4% on budesonide and 43.5% on placebo (p = 0.0582). All clinical secondary endpoints were in favour of budesonide. Budesonide decreased the number of soft or watery stools (16.3 vs. 7.7, p = 0.0186) and improved health-related quality of life for all four dimensions of the short health scale. Adverse events with a suspected relation to study drug were reported in one patient in the budesonide group and two patients in the placebo group. Neither serious nor severe adverse events occurred during the double-blind phase.

Conclusions: Budesonide decreased the frequency of soft or watery stools and improved the patients' quality of life significantly in MCi, but the primary endpoint was not met due to the low sample size (type 2 error). Budesonide was safe and well tolerated during the 8-weeks treatment course.

Ort, förlag, år, upplaga, sidor
Sage Publications, 2021
Nyckelord
budesonide, drug, incomplete microscopic colitis, induction therapy, MCi, microscopic colitis, QoL, quality of life, randomised clinical trial, watery diarrhoea
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-94002 (URN)10.1002/ueg2.12131 (DOI)000686519900001 ()34414678 (PubMedID)2-s2.0-85113157318 (Scopus ID)
Anmärkning

Funding Agency:

Dr Falk Pharma GmbH, Freiburg, Germany  

Tillgänglig från: 2021-09-01 Skapad: 2021-09-01 Senast uppdaterad: 2022-01-04Bibliografiskt granskad
Verhaegh, B. P. M., Münch, A., Guagnozzi, D., Wildt, S., Cebula, W., Diac, A. R., . . . Munck, L. K. (2021). Course of disease in patients with microscopic colitis: a European prospective incident cohort study. Journal of Crohn's & Colitis, 15(7), 1174-1183, Article ID jjab007.
Öppna denna publikation i ny flik eller fönster >>Course of disease in patients with microscopic colitis: a European prospective incident cohort study
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2021 (Engelska)Ingår i: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 15, nr 7, s. 1174-1183, artikel-id jjab007Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND AND AIMS: The disease course of microscopic colitis (MC) is considered chronic but benign. However, this assumption is based on mainly retrospective studies, reporting on incomplete follow-up of selective cohorts. Systematic, prospective and unbiased data to inform patients and health care professionals on the expected course of the disease and real-life response to therapy are warranted.

METHODS: A prospective, pan-European, multi-center, web-based registry was established. Incident cases of MC were included. Data on patient characteristics, symptoms, treatment and quality of life were systematically registered at baseline and during real-time follow-up. Four disease course phenotypes were discriminated and described.

RESULTS: Among 381 cases with complete 1-year follow-up, 49% had a chronic active or relapsing disease course, 40% achieved sustained remission after treatment and 11% had a quiescent course. In general, symptoms and quality of life improved after 3 months of follow-up. A relapsing or chronic active disease course was associated with significantly more symptoms and impaired quality of life after 1 year.

CONCLUSIONS: A minority of MC patients follow a quiescent disease course with spontaneous clinical improvement, whereas the majority suffers a chronic active or relapsing disease course during the first year after diagnosis, with persisting symptoms accompanied by a significantly impaired quality of life.

Ort, förlag, år, upplaga, sidor
Oxford University Press, 2021
Nyckelord
Microscopic colitis, disease activity, disease course, prognosis, prospective cohort study, treatment
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-88485 (URN)10.1093/ecco-jcc/jjab007 (DOI)000733846400012 ()33433605 (PubMedID)2-s2.0-85104091819 (Scopus ID)
Tillgänglig från: 2021-01-13 Skapad: 2021-01-13 Senast uppdaterad: 2022-01-04Bibliografiskt granskad
Miehlke, S., Guagnozzi, D., Zabana, Y., Tontini, G. E., Fiehn, A.-M. K., Wildt, S., . . . Munch, A. (2021). European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations. United European Gastroenterology journal, 9(1), 13-37
Öppna denna publikation i ny flik eller fönster >>European guidelines on microscopic colitis: United European Gastroenterology (UEG) and European Microscopic Colitis Group (EMCG) statements and recommendations
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2021 (Engelska)Ingår i: United European Gastroenterology journal, ISSN 2050-6406, E-ISSN 2050-6414, Vol. 9, nr 1, s. 13-37Artikel, forskningsöversikt (Refereegranskat) Published
Abstract [en]

Introduction: Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder.

Methods: Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method.

Results: These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice.

Conclusion: These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis.

Ort, förlag, år, upplaga, sidor
Sage Publications, 2021
Nyckelord
Microscopic colitis, inflammatory bowel disease, diarrhoea, budesonide
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-85421 (URN)10.1177/2050640620951905 (DOI)000561598100001 ()32819215 (PubMedID)2-s2.0-85089703028 (Scopus ID)
Anmärkning

Funding Agency:

UEG Activity Grant

Tillgänglig från: 2020-09-07 Skapad: 2020-09-07 Senast uppdaterad: 2023-06-01Bibliografiskt granskad
Lushnikova, A., Bohr, J., Wickbom, A., Münch, A., Sjöberg, K., Hultgren, O., . . . Hultgren Hörnquist, E. (2021). Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls. Frontiers in Medicine, 8, Article ID 727412.
Öppna denna publikation i ny flik eller fönster >>Patients With Microscopic Colitis Have Altered Levels of Inhibitory and Stimulatory Biomarkers in Colon Biopsies and Sera Compared to Non-inflamed Controls
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2021 (Engelska)Ingår i: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, artikel-id 727412Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Introduction: Microscopic colitis (MC) is an inflammatory bowel condition with two subtypes, lymphocytic colitis (LC) and collagenous colitis (CC). Unlike patients with ulcerative colitis (UC) and non-inflamed individuals, MC patients have reduced risk of developing colorectal cancer, possibly due to increased immune surveillance in MC patients.

Aim: To examine differences in levels of immunomodulatory molecules, including those involved in immune checkpoint mechanisms, in sera from patients with MC and in colonic biopsies from patients with MC and UC compared with controls.

Methods: Using Luminex, 23 analytes (4-1BB, 4-1BBL, APRIL, BAFF, BTLA, CD27, CD28, CD80, CTLA-4, E-cadherin, Galectin-3, GITR, HVEM, IDO, IL-2Rα, LAG-3, MICA, MICB, PD-1, PD-L1, PD-L2, sCD40L and TIM-3) were studied in serum from patients with active MC (n = 35) and controls (n = 23), and in colonic biopsies from patients with active LC (n = 9), active CC (n = 16) and MC in histological remission (LC n = 6, CC n = 6), active UC (n = 15) and UC in remission (n = 12) and controls (n = 58).

Results: In serum, IDO, PD-1, TIM-3, 4-1BB, CD27, and CD80 were decreased whereas 4-1BBL and IL-2Rα were increased in MC patients compared with controls. In contrast, in biopsies, levels of PD-L2 and 4-1BB were increased in MC and UC patients with active disease. Furthermore, in biopsies from CC and UC but not LC patients with active disease, CTLA-4, PD-1, APRIL, BAFF, and IL-2Rα were increased compared with controls. PD-L1 was increased in CC but not UC or LC patients. CD27 and TIM-3 were decreased in biopsies from MC patients in comparison to controls whereas levels of MICB were decreased in patients with active UC compared with controls.

Conclusions: Compared with non-inflamed controls, levels of soluble and membrane-bound immunomodulatory molecules were systemically and locally altered in MC and UC patients, with most analytes being decreased in serum but enhanced in colonic biopsies. These findings contribute to knowledge about checkpoint molecules and their role as biomarkers in MC and may also contribute to knowledge about possible mechanisms behind the seemingly protective effects of MC against colorectal cancer.

Ort, förlag, år, upplaga, sidor
Frontiers Media S.A., 2021
Nyckelord
Colonic biopsies, colorectal cancer, immune checkpoints, immune surveillance, microscopic colitis, serum, ulcerative colitis
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-95302 (URN)10.3389/fmed.2021.727412 (DOI)000715085000001 ()34722568 (PubMedID)2-s2.0-85118304770 (Scopus ID)
Anmärkning

Funding agencies:

Faculty of Medicine and Health, Örebro University

Örebro University Hospital Research Foundation OLL 926161 OLL-960784

Tillgänglig från: 2021-11-03 Skapad: 2021-11-03 Senast uppdaterad: 2022-02-08Bibliografiskt granskad
Holster, S., Rode, J., Bohr, J., Kumawat, A. K., Veress, G., Hultgren Hörnquist, E., . . . König, J. (2020). Faecal microbiota transfer in patients with microscopic colitis: a pilot study in collagenous colitis. Scandinavian Journal of Gastroenterology, 55(12), 1454-1466
Öppna denna publikation i ny flik eller fönster >>Faecal microbiota transfer in patients with microscopic colitis: a pilot study in collagenous colitis
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2020 (Engelska)Ingår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 55, nr 12, s. 1454-1466Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Objectives: Faecal microbiota transfer (FMT) consists of the infusion of donor faecal material into the intestine of patients with the aim to restore a disturbed gut microbiota.

Methods: In this pilot study (NCT03275467), the effect of three repeated FMTs (day 0, two weeks, four weeks) was studied and followed up for six months in nine collagenous colitis (CC) patients, using two stool donors.

Results: Five patients had an active disease at the time of baseline sampling. The primary endpoint (remission at six weeks, defined as <3 stools whereof <1 watery stool per day) was achieved by two of these patients, and by one at eight weeks. Overall, in all nine patients, FMT did not result in a significant reduction of watery stools, assessed by daily diary. However, diarrhoea (assessed by gastrointestinal symptom rating scale) was significantly improved at four (p = .038) and eight weeks (p = .038), indigestion at eight (p = .045) and 12 weeks (p = .006), disease-related worries at four (p = .027) and eight weeks (p = .027), and quality of life at six months (p = .009). FMT resulted in an increased number of lamina propria lymphocytes, possibly indicating an initial mucosal immune activation. No serious adverse events, no systemic effects, and no changes in faecal calprotectin and psychological symptoms were observed.

Conclusions: FMT is able to improve symptoms in a yet undefined subset of CC patients. Further studies could help to characterise this subset and to understand if these results can be generalised to all microscopic colitis patients.

Ort, förlag, år, upplaga, sidor
Taylor & Francis, 2020
Nyckelord
Faecal microbiota transplantation, microscopic colitis, collagenous colitis, gut microbiota
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-87120 (URN)10.1080/00365521.2020.1839544 (DOI)000584733600001 ()33142068 (PubMedID)2-s2.0-85095747650 (Scopus ID)
Anmärkning

Funding Agency:

Faculty of Medicine and Health, Örebro University, Sweden

Tillgänglig från: 2020-11-04 Skapad: 2020-11-04 Senast uppdaterad: 2022-09-12Bibliografiskt granskad
Larsson, J. K., Dabos, K. J., Höglund, P., Bohr, J., Münch, A., Giannakou, A., . . . Sjöberg, K. (2019). Cancer Risk in Collagenous Colitis. Journal of Clinical Medicine, 8(11), Article ID 1942.
Öppna denna publikation i ny flik eller fönster >>Cancer Risk in Collagenous Colitis
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2019 (Engelska)Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 8, nr 11, artikel-id 1942Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Data on malignancy in patients with collagenous colitis (CC) is scarce. We aimed to determine the incidence of cancers in patients with CC. In a two-stages, observational study, data on cancers in patients diagnosed with CC during 2000-2015, were collected from two cohorts. The risk was calculated according to the age-standardized rate for the first cohort and according to the standardized incidence ratio for the second cohort. The first cohort comprised 738 patients (394 from Scotland and 344 from Sweden; mean age 71 +/- 11 and 66 +/- 13 years, respectively). The incidence rates for lung cancer (RR 3.9, p = 0.001), bladder cancer (RR 9.2, p = 0.019), and non-melanoma skin cancer (NMSC) (RR 15, p = 0.001) were increased. As the majority of NMSC cases (15/16) came from Sweden, a second Swedish cohort, comprising 1141 patients (863 women, mean age 65 years, range 20-95 years) was collected. There were 93 cancer cases (besides NMSC). The risk for colon cancer was decreased (SIR 0.23, p= 0.0087). The risk for cutaneous squamous cell carcinoma was instead markedly increased (SIR 3.27, p = 0.001).

Ort, förlag, år, upplaga, sidor
MDPI, 2019
Nyckelord
colon cancer, cancer risk, collagenous colitis, lung cancer, microscopic colitis, skin cancer, squamous cell carcinoma
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:oru:diva-79137 (URN)10.3390/jcm8111942 (DOI)000502294400185 ()31718057 (PubMedID)2-s2.0-85082327847 (Scopus ID)
Anmärkning

Funding Agency:

Southern Health Care Region in Sweden 

Tillgänglig från: 2020-01-15 Skapad: 2020-01-15 Senast uppdaterad: 2023-12-08Bibliografiskt granskad
Carstens, A., Dicksved, J., Nelson, R., Lindqvist, C. M., Andreasson, A., Bohr, J., . . . Halfvarson, J. (2019). The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis. Clinical and Translational Gastroenterology, 10(7), Article ID e00065.
Öppna denna publikation i ny flik eller fönster >>The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis
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2019 (Engelska)Ingår i: Clinical and Translational Gastroenterology, E-ISSN 2155-384X, Vol. 10, nr 7, artikel-id e00065Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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

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

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

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

Ort, förlag, år, upplaga, sidor
Nature Publishing Group, 2019
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-75573 (URN)10.14309/ctg.0000000000000065 (DOI)000478837900001 ()31343467 (PubMedID)2-s2.0-85070852572 (Scopus ID)
Tillgänglig från: 2019-08-09 Skapad: 2019-08-09 Senast uppdaterad: 2023-12-08Bibliografiskt granskad
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
Öppna denna publikation i ny flik eller fönster >>Family history, comorbidity, smoking and other risk factors in microscopic colitis: a case-control study
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2017 (Engelska)Ingår i: European Journal of Gastroenterology and Hepathology, ISSN 0954-691X, E-ISSN 1473-5687, Vol. 29, nr 5, s. 587-594Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Lippincott Williams & Wilkins, 2017
Nyckelord
inflammatory bowel diseases; microscopic colitis; risk factors; smoking
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-57572 (URN)10.1097/MEG.0000000000000832 (DOI)000398812100015 ()28350750 (PubMedID)2-s2.0-85016730155 (Scopus ID)
Forskningsfinansiär
Svenska läkaresällskapet
Anmärkning

Other funding Agencies:

Örebro University Hospital Research Foundation (Nyckelfonden)

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

Örebro County Research Committee

Tillgänglig från: 2017-05-04 Skapad: 2017-05-04 Senast uppdaterad: 2020-12-01Bibliografiskt granskad
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
Öppna denna publikation i ny flik eller fönster >>Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
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2017 (Engelska)Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, nr 6, s. 932-945Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Lippincott Williams & Wilkins, 2017
Nyckelord
collagenous colitis, lymphocytic colitis, next-generation sequencing, ulcerative colitis, T-cell repertoire analysis
Nationell ämneskategori
Gastroenterologi
Identifikatorer
urn:nbn:se:oru:diva-59319 (URN)10.1097/MIB.0000000000001127 (DOI)000405609200014 ()28498152 (PubMedID)2-s2.0-85019705487 (Scopus ID)
Anmärkning

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 

Tillgänglig från: 2017-08-25 Skapad: 2017-08-25 Senast uppdaterad: 2020-12-01Bibliografiskt granskad
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