RMD Open | 2021
Association between T follicular helper cells and T peripheral helper cells with B-cell biomarkers and disease activity in primary Sjögren syndrome
Abstract
© Author(s) (or their employer(s)) 2021. Reuse permitted under CC BYNC. No commercial reuse. See rights and permissions. Published by BMJ. INTRODUCTION Primary Sjögren syndrome (pSS) is a systemic autoimmune disease, characterised by an infiltration of the exocrine glands, leading to sicca syndrome. Extraglandular systemic involvements (such as pulmonary, renal or neurological involvement) occur in about 30% of the patients. One of the most severe complications is the development of B cell lymphoma. pSS is characterised by chronic B cell activation, as evidenced by the presence of antiSSA (Sjögren syndrome A antigen), antiSSB (Sjögren syndrome B antigen) antibodies, rheumatoid factor (RF) and hypergammaglobulinaemia. Using mass cytometry (CyTOF), we have shown an expansion of plasma cells in minor salivary gland and an expansion of circulating plasmablasts in pSS patients, compared with controls. Ectopic germinal centres (EGC) in minor salivary glands are present in about onequarter of the patients and could enhance local production of autoantibodies. T cells also participate to the pathophysiology of pSS, as suggested by the presence of a T lymphocyte infiltrate within the patients minor salivary gland biopsies, as well as the association of pSS with several HLA class II alleles. In addition, there is an association between pSS and a singlenucleotide polymorphisme located within CXCR5 locus that codes for a key chemokine expressed by T follicular helper (Tfh) cells. Tfh are a subset of T lymphocytes specialised in providing help to B cells, and are essential for EGC formation, recruitment (via CXCL13) and activation (via ICOS) of B cells, affinity maturation and development of memory B cells and plasmablasts (via secretion of interleukin 21 (IL-21)). They are CXCR5, PD-1 and ICOS, the latter being considered as an activation marker. Several studies supported their involvement in pSS: (1) increased levels of Tfh in blood and within minor salivary glands in pSS compared with controls, (2) correlation between activated Tfh and disease activity (ESSDAI (EULAR Sjögren s syndrome disease activity index), 10 clinESSDAI), (3) correlation between IL-21 and disease activity and autoantibodies status 11 12 and (4) ability of the epithelial cells to induce Tfh. Another T cell subset has been recently described in inflamed tissues such as joint, but also in the blood of patients with rheumatoid arthritis: the T peripheral helper cells (Tph) that are characterised by CD4PD1CXCR5. In contrast to Tfh, these cells lack CXCR5 but similar to Tfh, they express IL-21, CXCL13, ICOS and induce plasmablasts differentiation in vitro. In SLE, their expansion correlates with disease activity. 15 Two studies have shown that circulating Tph were higher in patients with pSS compared with controls. 16 Key messages