Proportion of T follicular helper cells in peripheral blood of rheumatoid arthritis patients: a systematic review and meta-analysis

Abstract

Objectives: Follicular helper T (Tfh) cells have critical roles in the development and promotion of humoral immune responses. Accumulating evidence points to alterations in the levels and activity of Tfh which may lead to impaired immune tolerance and development of antibody-mediated autoimmune diseases, such as rheumatoid arthritis (RA). To elucidate the status of Tfh cells in patients with RA, we conducted a systematic review and meta-analysis to assess the proportion and types of Tfh cells in the PB of RA patients.Method: We systematically searched databases of Embase, Pubmed, Web of sciences (WOS), and Scopus to identify the eligible articles. We performed meta-analysis to assess the proportion of Tfh cells in PB of RA patients compared to healthy controls (HCs). We also assessed the proportion of Tfh cells based on different parameters including Tfh de nition markers, disease activity status, disease stage, treatment status, serum markers, and the geographical location of the included articles.Results: Regardless of de nition markers, the proportion of Tfh cells in RA patients was signi cantly higher than that in HCs (SMD 0.75, [0.56, 0.93], p<0.0001). Based on subgroup analyses, the proportion of Tfh cells with the individual de nitions were also signi cantly higher in PB of RA patients compared to HCs. Tfh cells proportion in untreated-RA and early-RA patients was markedly greater than HCs, when comparisons were made without considering the de nition markers, and also when Tfh cells was de ned by the speci ed de nition markers. While the proportion of Tfh cells by all de nitions was signi cantly higher in active-and remission-RA compared to HCs, individual analysis of two de nitions, CD4 + CXCR5 + and CD4 + CXCR5 + ICOS + , didn't show signi cant differences. In addition, higher proportion of Tfh cells de ned by all de nitions as well as a speci ed de nition (CD4 + CXCR5 + PD-1 high ) was observed when S + RA and S -RA patients were compared to the HCs. Higher Tfh cells proportion in RA patients compared with HCs was observed in the Asian populations (SMD 0.89, [0.68, 1.09], p<0.0001), while there was a trend toward signi cant in the proportion of Tfh between the two groups in non-Asians (SMD 0.29, [-0.003, 0.59], p=0.052). Conclusion:Altogether, our results demonstrate that circulating Tfh are highly elevated in RA patients and are also signi cantly increased in untreated-, early-and S + -RA patients, underscoring the potential pathogenic role of this cell population in RA and its potential use as a biomarker and a target for RA therapy.HCs. Hence, in the present work, we systematically searched and reviewed the available studies documenting the proportion of Tfh among CD4 + T cells in PB of RA patients, and conducted a meta-analysis to elucidate the proportion of Tfh cells in the PB of RA patients compared to the HCs. Materials And Methods Search StrategyThis study was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registe...

Follicular Helper T Cells and Autoimmune Diseases

“…Rheumatoid arthritis (RA) is a prevalent chronic autoimmune disease characterized by synovial inflammation and joint cartilage destruction, resulting in joint deformity and disability [24]. It was found that the proportion of cTfh cells in RA patients was significantly higher than that in healthy people [25] and the Tfh cells are increased in the synovium of patients with RA compared with patients with inflammatory osteoarthritis [26]. The frequencies of circulating CD4 + CXCR5 + CD40L + Tfh cells, a Tfh cell subpopulation, are positively correlated with disease activity score-28 with erythrocyte sedimentation rate (DAS28-ESR), rheumatoid factors (RFs), and anticyclic citrullinated peptide (anti-CCP) autoantibodies, which are of great significance in the pathogenesis of RA [27].…”

Increased frequency of TIGIT+ CD4 T Cell subset in autoantibody-positive first-degree relatives of patients with rheumatoid arthritis

“…As such, it has been proposed that an expanded pathogenic CD4 + T-cell population mediates activation of autoreactive B cell recognizing post-translationally modified self-antigens and resulting in the production of matured autoantibodies directed towards these autoantigens ( 4 , 5 ). These processes typically occur in germinal centers of lymphoid tissues and involve a well characterized population of T follicular helper cells (Tfh) expressing CXCR5 and PD-1 ( 6 ). Of considerable interest has been the demonstration of a distinct population of activated CD4+ T cells, both in the blood and the affected synovial tissues, characterized by PD-1 hi CXCR5 - expression, and labelled as peripheral-helper T cells (Tph cells) ( 7 ).…”