Relationships of circulating CD4+ T cell subsets and cytokines with the risk of relapse in patients with Crohn’s disease

Autor: Rémi Duclaux-Loras, Gilles Boschetti, Bernard Flourie, Xavier Roblin, Jean-Benoit Leluduec, Stéphane Paul, Thibaut Almeras, Karine Ruel, Anthony Buisson, Jacques Bienvenu, Cendrine Josson, Renaud Jasnowski, Stéphane Legastelois, Arnaud Foussat, Camille Meunier, Christophe Viret, Aurore Rozieres, Mathias Faure, Dominique Kaiserlian, Stéphane Nancey
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Immunology, Vol 13 (2022)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2022.864353
Popis: Background and aimsWe aimed to analyze circulating CD4+ T cell subsets and cytokines during the course of Crohn’s disease (CD).Methods and resultsCD4+ T cell subsets, ultrasensitive C-reactive protein (usCRP), and various serum cytokines (IL-6, IL-8, IL-10, IL-13, IL-17A, IL-23, TNFα, IFNγ, and TGFβ) were prospectively monitored every 3 months for 1 year, using multicolor flow cytometry and an ultrasensitive Erenna method in CD patients in remission at inclusion. Relapse occurred in 35 out of the 113 consecutive patients (31%). For patients in remission within 4 months prior to relapse and at the time of relapse, there was no significant difference in Th1, Th17, Treg, and double-positive CD4+ T cell subsets co-expressing either IFNγ and FOXP3, IL-17A and FOXP3, or IFNγ and IL-17A. On the contrary, in patients who remained in remission, the mean frequency and number of double-positive IL-17A+FOXP3+ CD4+ T cells and the level of usCRP were significantly higher (p ≤ 0.01) 1 to 4 months prior to relapse. At the time of relapse, only the IL-6 and usCRP levels were significantly higher (p ≤ 0.001) compared with those patients in remission. On multivariate analysis, a high number of double-positive IL-17A+FOXP3+ CD4+ T cells (≥1.4 cells/mm3) and elevated serum usCRP (≥3.44 mg/L) were two independent factors associated with risk of relapse.ConclusionsDetection of circulating double-positive FOXP3+IL-17A+ CD4+ T cell subsets supports that T cell plasticity may reflect the inflammatory context of Crohn’s disease. Whether this subset contributes to the pathogenesis of CD relapse needs further studies.
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