Higher frequencies of circulating ICOS+, IL-21+ T follicular helper cells and plasma cells in patients with new-onset membranous nephropathy

T follicular helper (TFH) cells and B cells are known to regulate humoral immune responses. This study is aimed at examining the putative contribution of different subsets of circulating of TFH cells and B cells to membranous nephropathy (MN).A total of 45 MN patients and 19 healthy controls (HCs) were examined for the number of TFH cells and B cells by flow cytometry. The level of 24-h urinary protein and eGFR were calculated, and the level of serum cytokines was examined. The potential association among these measures was analyzed.Compared to the HCs, MN patients had significantly higher numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+CD154+, CD4+CXCR5+IL-21+, and CD4+CXCR5+CD28+ TFH cells, as well as IgD+CD27-CD19+ and CD138+CD19+ B cells. However, the number of IgD+CD27+CD19+ B cells was significantly lower in MN patients than in the HC. The levels of serum IL-21, IL-2, IL-4, IL-10, IL-17A, and IFN-γ were significantly higher in MN patients than in the HC. Furthermore, the numbers of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+CD154+, CD4+CXCR5+IL-21+, CD4+CXCR5+CD28+ TFH cells, CD138+CD19+ B cells, and the level of sera IL-21 were negatively correlated with the values of eGFR, but positively correlated with the levels of 24-h urinary proteins. Following treatment, the numbers of CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+CD154+, CD4+CXCR5+IL-21+, CD4+CXCR5+CD28+ TFH cells, CD138+CD19+ B cells, and the levels of IL-21 were significantly reduced. In contrast, IL-4 and IL-10 levels were noticeably increased after treatment.Data suggest that activated TFH and plasma cells may contribute to the pathogenesis of MN.