In comparison with HC, significantly higher percentages of circulating IgD+CD27−CD19+ naive B, CD86+CD19+ and CD95+CD19+ activated B, CD3+CD4+CXCR5+,

CD3+CD4+CXCR5+ICOS+, CD3+CD4+CXCR5+PD-1+ and CD3+CD4+CXCR5+ICOS+PD-1+ Tfh cells but lower IgD+CD27+CD19+ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL-21 in the RA patients. Furthermore, the percentages of CD95+ B cells were correlated positively with the frequency of PD-1+ Tfh cells, but negatively with ICOS+ Tfh cells. The percentages of CD86+ B cells and ICOS+ Tfh cells were correlated positively with the values of disease activity score 28 (DAS28). Following the drug therapies for 1 month, the percentages Imatinib datasheet of CD86+ B and PD-1+ Tfh cells were reduced significantly in the drug-responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers

for evaluating the therapeutic responses of individual patients with RA. Rheumatoid arthritis (RA) is a severe chronic autoimmune inflammatory disease. RA is characterized by symmetric polyarthritis associated with pain and swelling in multiple joints. Importantly, most RA patients eventually develop cartilage lesions and bone destruction, leading to functional incapacity. In addition, RA patients are affected by an increased frequency of other co-morbidities

and decreased life expectancy [1]. Currently, the pathogenic process of RA is still unclear. The pathogenesis of RA is attributed https://www.selleckchem.com/autophagy.html to the interaction of many types of immunocompetent cells, such as antigen-specific T and B cells, aberrant activation of antigen-presenting cells (APC) and autoantibodies [2]. Although antigen-specific Thiamet G T cells are crucial for the pathogenesis of RA, recent evidence suggests that B cells play an important role in the development and progression of RA [3]. CD27 is expressed on somatically mutated B cells and the distinct subsets of B cells can be defined as naive immunoglobulin (Ig)D+CD27−, preswitch memory IgD+CD27+, post-switch memory IgD−CD27+ and double-negative IgD−CD27− B cells [4, 5]. Activation of B cells up-regulates CD86, CD95 and major histocompatibility complex (MHC) class II expression and some activated B cells differentiate into plasma cells which express CD38 [6], while others become memory B cells which express CD27 [5]. The up-regulated CD95 expression in activated B cells makes them sensitive to ligand-mediated apoptosis [7, 8]. However, little is known about the frequency of these different subsets of activated B cells in patients with new-onset RA. The activation and functional differentiation of B cells are regulated by CD4+ T cells, particularly by T follicular helper (Tfh) cells [9, 10].