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Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
Örebro universitet, Institutionen för medicinska vetenskaper. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.ORCID-id: 0000-0002-9635-0341
Örebro universitet, Institutionen för medicinska vetenskaper. Nutrition-Gut-Brain Interactions Research Centre, Örebro University, Örebro, Sweden.ORCID-id: 0000-0002-7173-5579
Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Pathology, Örebro University Hospital, Örebro, Sweden.ORCID-id: 0000-0003-2317-5738
Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Medicine, Div. of Gastroenterol., Örebro University Hospital, Örebro, Sweden.ORCID-id: 0000-0002-0942-0816
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2017 (engelsk)Inngår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 23, nr 6, s. 932-945Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
Lippincott Williams & Wilkins, 2017. Vol. 23, nr 6, s. 932-945
Emneord [en]
collagenous colitis, lymphocytic colitis, next-generation sequencing, ulcerative colitis, T-cell repertoire analysis
HSV kategori
Identifikatorer
URN: urn:nbn:se:oru:diva-59319DOI: 10.1097/MIB.0000000000001127ISI: 000405609200014PubMedID: 28498152Scopus ID: 2-s2.0-85019705487OAI: oai:DiVA.org:oru-59319DiVA, id: diva2:1136029
Merknad

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 

Tilgjengelig fra: 2017-08-25 Laget: 2017-08-25 Sist oppdatert: 2018-09-04bibliografisk kontrollert

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Gunaltay, SezinRepsilber, DirkHelenius, GiselaNyhlin, NilsBohr, JohanHultgren, OlofHultgren Hörnquist, Elisabeth

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