SEARCH

SEARCH BY CITATION

Abstract

IgA nephropathy (IgAN) diagnosis remains largely based upon immunohistologic detection of IgA- and IgG-containing glomerular deposits in renal mesangial cells, and little is known about the underlying pathogenic mechanisms. This study examines the putative contribution of B cell types, including the Breg type, to IgAN pathogenesis. Twenty-four patients with IgAN and proteinuria (Group A: <3.5 g/24 h, n = 13; Group B: >3.5 g/24 h, n = 11) and 10 healthy controls were enrolled. The frequencies of B cell subtypes in venous blood were measured by flow cytometry. Galactose-deficient IgA1 was measurement by ELISA. Needle biopsies were analysed by histology and immunofluorescence microscopy. Correlation between clinical features and B cell subtypes, including the regulatory B (Breg) cells, and Breg cell-derived immunomodulatory cytokine IL-10 was assessed by Spearman's rank correlation test. IgAN patients had significantly higher frequencies of CD27+CD19+, CD38+CD19+, CD86+CD19+ and CD5+CD19+ B cells than the healthy controls, but significantly lower levels of Breg cells and intracellular expression of IL-10 protein in the Breg subtype. Serum IgA concentration positively correlated with CD27+CD19+ B cell frequency and negatively correlated with IL-10+ Breg cell frequency in IgAN patients, and the percentage of CD19+CD5+CD1d+ in CD19+ cells was negatively correlated with the level of serum Gd-IgA1. Furthermore, the frequencies of CD19+CD38+ and CD19+CD86+ in the CD19+ subpopulation negatively correlated with the estimated glomerular filtration rate of IgAN patients. Several of the CD19+ B cell subtypes and the IL-10+ Breg cells are differentially expressed in IgAN patients and may contribute to the disease pathogenesis.