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

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was funded by the National Natural Science Foundation of China (No. 30972610 and 81273240), Jilin Province Science and Technology Agency (No.20160101037JC and 20170622009JC), the Health Department Research Projects of Jilin Province (2017C021), and Norman Bethune Program of Jilin University (2012206).