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

Abstract

Background: 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). Methods: 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. Results: 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. Conclusions: Data suggest that activated TFH and plasma cells may contribute to the pathogenesis of MN.

Keywords

• tfh cells
• b cells
• membranous nephropathy