P039/O03 Circulating follicular helper T cells are increased in systemic sclerosis and promote plasmablast differentiation through the IL-21 pathway which can be inhibited by ruxolitinib. (March 2019)

• Record Type: Journal Article
• Authors: Ricard, L; Jachiet, V; Malard, F; Ye, Y; Stocker, N; Rivière, S; Senet, P; Monfort, J-B; Fain, O; Mohty, M; Gaugler, B; Mekinian, A
• Is Part Of: Annals of the rheumatic diseases. Volume 78(2019)Supplement 1
• Page Start: A15
• Page End: A15
• Publication Date: 2019-03
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-EWRR2019.31
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Career situation of first and presenting author: Student for a master or a PhD Introduction: Systemic sclerosis (SSc) is an autoimmune disease characterized by widespread fibrosis, microangiopathy and autoantibodies. Follicular helper T (Tfh) cells CD4 + CXCR5 + PD-1 + cooperate with B lymphocytes to induce the differentiation of plasmocytes secreting Immunoglobulins (Ig). Circulating Tfh (cTfh) cells are increased in several autoimmune diseases. 1 Tfh cells can infiltrate the skin of SSc patients, and induce fibrosis in vitro . 2 Objectives: The aim of this study was to perform a quantitative and functional analysis of cTfh cells in SSc. Methods: Using flow cytometry, we analyzed cTfh cells from 52 SSc patients with no immodulotary treatment and 38 healthy controls (HC). In vitro coculture experiments of sorted cTfh and B cells from 13 SSc patients and 6 HC were performed for functional analysis. IgG and IgM production were measured by ELISA. BCL-6, Blimp-1, CXCL13 and IL-21 expression were analyzed by RTqPCR. Results: We observed that cTfh cell numbers are increased in SSc patients compared with HC. Furthermore, the increase in cTfh cells was more potent in patients with severe forms of SSc such as diffuse SSc and in the presence of arterial pulmonary hypertension. cTfh cells from SSc patients present an activated Tfh phenotype, with high expression of BCL-6 and increased capacity to produce IL-21 in comparison to HC. In vitro, cTfh cells from SSc patients had higher capacity to stimulate the differentiation of CD19 + CD27 + CD38 hi B cells and their secretion of IgG and IgM through the IL-21 pathway than cTfh cells from HC. Blocking IL-21 or using the JAK1/2 inhibitor ruxolitinib reduced the Tfh cells' capacity to stimulate the plasmablasts and Ig production. Conclusions: Circulating Tfh cells are increased in SSc and correlate with SSc severity. The IL-21 pathway or JAK1/2 blockade by ruxolitinib could be a promising strategy in the treatment of SSc. References: Crotty S. T follicular helper cell differentiation, function, and roles in disease. Immunity 2014;41(4):529-42. Taylor DK, Mittereder N, Kuta E, Delaney T, Burwell T, Dacosta K, et al . T follicular helper-like cells contribute to skin fibrosis. Sci Transl Med 2018;10(431). Acknowledgements: This work was supported by the Aterhit foundation and received grants from 'Groupe Francophone de Recherche sur la Sclérodermie' (GFRS). Disclosure of Interest: None declared