Increased Frequency of Circulating Follicular Helper T Cells in Patients with Rheumatoid Arthritis

Abstract

Follicular helper T (Tfh) cells are recognized as a distinct CD4+ helper T-cell subset, which provides for B-cell activation and production of specific antibody responses, and play a critical role in the development of autoimmune disease. So far, only one study investigated the circulating Tfh cells increased in a subset of SLE patients. Since relatively little is known about the Tfh cells in rheumatoid arthritis (RA) patients, in this study, Tfh-cell frequency, related cytokine IL-21, and transcription factor Bcl-6 were investigated in 53 patients with RA and 31 health controls. Firstly, we found that the frequency of CD4+CXCR5+ICOShigh Tfh cells was increased significantly in the peripheral blood of RA patients, compared with that in healthy controls. It is known that Tfh cells are critical for directing the development of an antibody response by germinal centers B cells; secondly, we observed that the Tfh-cell frequency is accompanied by the level of anti-CCP antibody in RA patients. Furthermore, expression of Bcl-6 mRNA and plasma IL-21 concentrations in RA patients was increased. Taken together, these findings have shown that the increased frequency of circulating Tfh cells is correlated with elevated levels of anti-CCP antibody, indicating the possible involvement of Tfh cells in the disease progression of RA.

Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome

“…Another important transcription factor [14]. Serum levels of IL-21 cytokine were found to be elevated in autoimmune thyroiditis and RA patients [31,32]. In our study, not every patient had …”

The darker side of follicular helper T cells: from autoimmunity to immunodeficiency

“…The alteration of T FHC cells has been reported in patients with various autoimmune diseases, such as rheumatoid arthritis, primary Sjogren's syndrome, juvenile dermatomyositis and autoimmune thyroid diseases, where T FHC cells are present at a higher frequency and show positive correlation with serum autoantibody titer in the patients. [52][53][54][55] Overall, these observations suggest an important role for T FHC cells in human autoimmunity. However, it should be noted that although T FHC cells resemble T FH cells in terms of ICOS and PD-1 expression, T FHC cells in SLE patients do not express Bcl6 and IL-21 that are hallmarks of classic T FH cells.…”

“…50 Recent studies have further provided clearer evidence on the role of T FH cells in promotion of both systemic and organ-specific autoimmune diseases in humans. [51][52][53][54][55] Simpson et al 51 performed an elegant study investigating the role of T FH cells in patients with SLE and Sjogren's syndrome. They found an overrepresented population of CD4 1 CXCR5 1 T FH cell-like cells in the blood, referred to as circulating T FH (T FHC ) cells, of a subset of the SLE patients (14 out of 46), which expressed ICOS and PD-1 compared with healthy controls.…”

“…The patients deficient in ICOS and CD40L lack T FHC cells, whereas T FHC cells expressing ICOS are overrepresented in SLE and rheumatoid arthritis patients. 10,51,53 T FH CELLS AND IMMUNODEFICIENCY Immunodeficiency is a pathological condition where the immune response is compromised or absent. Defects in humoural immune response lead to the humoral immunodeficiencies, such as common variable immunodeficiency (CVID), X-linked hyper IgM syndrome (HIGM) and X-linked lymphoproliferative disease (XLP).…”

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

“…Tfh cells can enter the follicle and secrete cytokines and other molecules to help the formation of germinal centre (GC), high-affinity long-living plasma cells and memory B cells [15,16]. A previous study has shown a higher frequency of Tfh cells and increased levels of anti-CCP antibodies in patients with new-onset RA [17].…”