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High Serum sCD40 and a Distinct Colonic T Cell Profile in Ulcerative Colitis Associated With Primary Sclerosing Cholangitis
Umeå University, Faculty of Medicine, Department of Medical Biosciences.
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2019 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 13, no 3, p. 341-350Article in journal (Refereed) Published
Abstract [en]

Background and Aims: There is a strong association between primary sclerosing cholangitis [PSC] and ulcerative colitis [UC], but the immunological link between the two diseases is obscure. We compared serum cytokine profiles of patients with PSC-UC and UC, and investigated a number of selected cytokines in colonic biopsy samples. We also assessed the presence and activation of T cells in peripheral blood and colonic mucosa.

Methods: Serum samples from 22 patients with PSC-UC, 28 patients with UC, and 19 controls were analysed by a proximity extension assay including 92 inflammatory cytokines. Biopsies from caecum, sigmoid colon, and rectum were collected from the same patients. Quantitative analysis for IFN-, IL-2, IL-4, IL-5, IL-13, IL-17A/ E/F, IL-21, IL-22, IL-23, and IL-27 was carried out on tissue homogenates. T cell phenotype was evaluated by flow cytometry.

Results: By multivariate analysis we identified a cluster of serum cytokines with higher levels in PSC-UC, and sCD40 in particular was strongly associated with this patient group. In contrast, colonic cytokines were only modestly increased in PSC-UC, whereas several Th1-, Th2-, and Th17-associated cytokines were increased in UC. Patients with PSC-UC had increased colonic levels of CXCR3-positive CD8(+) T cells but fewer CD25-positive CD4(+) T cells. An increased CRTH2/CXCR3-quote indicated a predominance of Th-2 type CD4(+) T cells in UC patients.

Conclusions: Our study reveals different cytokine profiles and T cell profiles in PSC-UC and UC, with higher systemic levels of cytokines in PSC-UC, and a more pronounced colonic inflammation in UC. Serum sCD40 could potentially be investigated as a marker for PSC in UC.

Place, publisher, year, edition, pages
Oxford University Press, 2019. Vol. 13, no 3, p. 341-350
Keywords [en]
Primary sclerosing cholangitis, cytokine, T cell
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:umu:diva-158605DOI: 10.1093/ecco-jcc/jjy170ISI: 000464942000011PubMedID: 30383225OAI: oai:DiVA.org:umu-158605DiVA, id: diva2:1314442
Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-05-08Bibliographically approved

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Wanders, Alkwin

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