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

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.