Clinically, most patients with primary nephrotic syndrome (PNS) have low serum IgG levels, which is an important factor in infection and in PNS relapse.To some extent, the mechanisms involved remain largely unknown. Here, we aimed to investigate the pathogenesis of the decreased IgG levels in PNS. Peripheral blood was collected from patients with PNS and closely age- and sex-matched healthy individuals. The frequency, phenotype and molecular function of different circulating B cell and T follicular helper cell (TFH) subsets were examined by flow cytometry. The function of the CD40/CD40 L interaction in immunoglobulin class-switch recombination (CSR) was evaluated by assessing the induction of activation-induced deaminase (AID) expression with CD40 L stimulation. We revealed an increase in the levels of circulating total plasmablasts, plasma cells and mature-naive B cells and a decrease in the levels of germinal centre-like B cells and CD19+IgG+ B cells in PNS. In addition, although the expression of CD86 on the surface of B cells and the expression of the inducible costimulator (ICOS) on the surface of TFH cells both were increased, the expression of CD40 L on the surface of TFH cells was decreased. Moreover, upon stimulation with CD40 L in vitro, the mRNA expression of AID in peripheral blood mononuclear cells (PBMCs) was decreased in patients with PNS compared with that in healthy controls. Our results indicate that the immunoglobulin CSR of B cells was partly dysfunctional and provide insights into the potential involvement of impaired TFH cell-dependent B cell responses in the pathogenesis of low IgG levels through downregulating CD40 L expression on TFH cells in PNS.
Keywords: CD40 ligand; Class-Switch recombination; Follicular helper T cells; Low IgG; Primary nephrotic syndrome.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.