Role of IgG autoantibodies in the pathogenesis of IgA nephropathy assessed in a passive mouse model

IgA nephropathy (IgAN), the most common primary glomerulonephritis worldwide, is characterized by IgA1-containing glomerular immunodeposits. These immunodeposits are thought to originate from the circulating immune complexes consisting of aberrantly glycosylated IgA1 (galactose-deficient IgA1; Gd-IgA1) bound by IgG autoantibodies. This hypothesis is supported by the findings that renal immunodeposits of IgA nephropathy patients are enriched for IgG autoantibodies specific for galactose-deficient IgA1 (Rizk et al., J. Am. Soc. Nephrol. 30(10), 2017-2026, 2019). However, experimental proof is needed. This study provides in vivo data in mice that support the pathogenic role of IgG autoantibodies in IgAN. Overall design: Kidneys of female CB-17 SCID (Balb/c background) were harvested after 3 doses of IgG-Gd-IgA1 immune complexes (administered i.v., one dose every other day, harvest one day after the third injection). Tissue was frozen in RNAlater. RNA extraction and RNA-Seq was performed by and sent to GeneWiz.