As shown in Fig. 2, the expression of PD-1 and IL-21 in either the active RA group (31.5 ± 2.1% and 4.9 ± 0.6%, respectively) or inactive RA group (26.5 ± 2.5% and 4.5 ± 0.5%, respectively) was significantly higher than that in the HCs (13.4 ± 0.8% and 2.7 ± 0.3%, respectively) (P < 0.05, Fig. 2a and c), while there was no difference observed in ICOS expression in circulating CD4+CXCR5+ T cells among the three groups (active RA, 15.5 ± 2.3%; inactive RA, 13.2 ± 1.2%; HCs, 12.3 ± 1.0%; P > 0.05, Fig. 2b). This evidence concerns the gene CD4 and rheumatoid arthritis.