Moreover, several studies have demonstrated that expanded frequencies of circulating ICOS+CXCR5+CD4+TFH cells and/or PD-1+CXCR5+CD4+TFH cells in various autoimmune diseases such as SLE, RA, ITP, and Sjögren's syndrome are positively associated with the autoantibodies production, TFH cells associated cytokines as IL-21, which aggravate the progression of those diseases [19, 25–28, 38]. This evidence concerns the gene IL21 and rheumatoid arthritis.