Background:Several studies have demonstrated that an immune dysregulation affecting both B and T cells occurs in rheumatoid arthritis (RA). Follicular helper T (Tfh) cells are crucial for B cell maturation, activation and class-switching as well as for germinal center (GC) formation, whereas follicular regulatory T (Tfr) cells can modulate the GC reaction by suppressing Tfh and B cells.Objectives:The main goal of this study was to analyze the phenotype and frequency of circulating follicular T cell subsets in established RA patients.Methods:Blood samples were collected from established RA patients with active disease, treated with methotrexate (n=32) and from a group of age and sex-matched healthy donors (n=11). Peripheral blood mononuclear cells (PBMC) were isolated and Tfh (CD4+CXCR5+CD45RO+) and Tfr (CD4+ CXCR5+CD25+FoxP3+) cells, as well as their three major subsets [CXCR3+CCR6- (Th1-like), CXCR3-CCR6- (Th2-like) and CXCR3-CCR6+ (Th17-like)] were evaluated by flow cytometry.Results:The frequency of circulating Tfh cells was similar between established RA patients and controls. Nonetheless, RA patients had a decreased frequency of Th1-like Tfh cells, and an increased frequency of Th2-like Tfh cells when compared to controls. No significant differences were observed in the frequencies of Th17-like Tfh cells between both groups. The frequency of circulating Tfr cells was significantly increased in RA patients in comparison to controls. Furthermore, Tfr cells from RA patients had significantly increased CD69 median fluorescence intensity (MFI) values when compared to controls. No significant differences were found in the percentages and MFI values of PD-1, ICOS, CD28, CTLA-4, CD40-L and HLA-DR expressed by Tfh and Tfr cells in RA patients when compared to controls.Conclusion:Established RA patients have increased circulating frequencies of Tfr cells, with higher CD69 expression levels, when compared to healthy controls. These results suggest a pre-activation state of Tfr cells in RA and a potential role in the disease physiopathology.*RA Moura, JE Fonseca and L Graca are joint senior authors.Disclosure of Interests:None declared