Phospholipase A2 Receptor and α-enolase in the Immunodiagnosis of membranous nephropathy

Abstract

M-type phospholipase A2 receptor (PLA2R) and α-enolase are two recently identified autoantigens in adult idiopathic membranous nephropathy (IMN). To identify their diagnostic value and the potential roles in the pathogenesis of MN, renal biopsies and sera from 23 patients with MN were investigated. In 19 IMN cases, the positivity for glomerular PLA2R and circulating anti-PLA2R antibodies was 47% and 26% respectively, while only 5% glomeruli showed positive α-enolase staining. IgG4 was often codominant with either IgG1 or IgG3 in PLA2R-positive glomeruli which also showed more prevalent and stronger C3 staining as compared with PLA2R-negative glomeruli. A positive correlation between IgG1 with complement C3C expression in glomeruli was observed. Circulating anti-PLA2R autoantibody titers and PLA2R expression in renal biopsies were associated with clinical outcomes (follow up proteinuria). The results indicate that in PLA2R related MN, autoantibody –antigen interaction activates complement C3 directly or indirectly, resulting in podocyte injury and proteinuria.