Increased ratio of ICOS+/PD-1+ follicular helper T cells positively correlates with the development of human idiopathic membranous nephropathy

To identify the frequencies of different subsets of peripheral blood follicular helper T (Tfh) cells in human idiopathic membranous nephropathy (IMN), 39 patients with new onset IMN and 18 age- and gender-matched healthy controls (HC) were enrolled for this study. The frequency of Tfh cells in venous blood were measured by flow cytometry, while concentration of serum IL-21 was detected by enzyme-linked immunosorbent assay. Correlation between the clinical features of IMN and Tfh cells was assessed by Spearman's rank correlation test. Overall, the frequencies of total, ICOS+, and PD-1(+) Tfh cells were increased in IMN patients, while the ratio of ICOS+/PD-1(+) Tfh cells positively correlated with IMN progression. However, the elevated serum IL-21 level in three subgroups of IMN patients, stratified based on 24-h urine protein levels, was not statistically significant compared to HC. Nonetheless, intracellular IL-21 in Tfh cells was generally increased in all IMN patients, and closely correlated with IMN development. Finally, the frequency of IL-21(+) Tfh cells and the ratio of ICOS+/PD-1(+) Tfh cells were positively correlated with the estimated 24-h urine protein of IMN patients. The data indicated that Tfh cells contribute to the pathogenicity of IMN. The ratio of ICOS+/PD-1(+) Tfh cells and the frequency of IL-21(+) Tfh cells may be indicators for evaluating the IMN development.