High Serum sCD40 and a Distinct Colonic T Cell Profile in Ulcerative Colitis Associated With Primary Sclerosing Cholangitis.
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Lampinen M, Vessby J, Fredricsson A, Wanders A, Rorsman F, Carlson M
J Crohns Colitis 13 (3) 341-350 [2019-03-26; online 2018-11-02]
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. 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-γ, 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. 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. 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.
Affinity Proteomics Uppsala [Service]
PLA and Single Cell Proteomics [Service]
PubMed 30383225
DOI 10.1093/ecco-jcc/jjy170
Crossref 10.1093/ecco-jcc/jjy170
pii: 5139660