The relationship of anti-phospholipase A2 receptor antibody and C5a complement with disease activity and short-term outcome in idiopathic membranous nephropathy

Abstract

Background: The binding of anti-phospholipase A2 receptor (anti-PLA2R) antibody to podocyte and complement activation is the mechanisms of idiopathic membranous nephropathy (IMN). C5a, a complement activation end product, is a strong inflammatory cell stimulator and can influence the behavior of T cells and dendritic cells. This study examined the etiology–disease relationship and significance of auto-antibody and C5a with short-term remission. Method: Plasma anti-PLA2R antibody and C5a were measured with the blood samples that were collected when patients were admitted for renal biopsy. The deposition of IgA, IgG, IgM, C1q and C3c in glomerulus was graded according to immunofluorescence staining. The relationship of anti-PLA2R antibody with C5a, glomerular immunoglobulin and complement deposition was examined. Antibody and C5a levels as predictors of short-term remission were also examined. Results: In 72 IMN patients, 50 patients had positive plasma anti-PLA2R antibody. The antibody had positive correlation to proteinuria. Patients with high grade IgG or C3c, but not IgA/IgM/C1q, deposition had higher anti-PLA2R antibody titers. C5a was increased in IMN patients, but had no correlation with anti-PLA2R antibody or proteinuria. The analysis revealed that C5a, not initial anti-PLA2R antibody, was a predictor associated with 12-month remission in patients receiving immunosuppression with multivariate-adjusted OR 0.74 (95% CI, 0.58–0.94, P = 0.01). Conclusion: This study provides indirect evidences of etiology–disease relationship of anti-PLA2R antibody in IMN patients. The role of C5a, a predictor of remission, in the disease course of MN and the influences on inflammatory cells in MN patients is worth to be clarified. Keywords: C5a, Disease activity, Membranous nephropathy, Anti-phospholipase A2 receptor antibody, Prognosis