IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study

The deposition of IgG4 of antibodies against phospholipase A2 receptor (anti-PLA₂R) is predominating in the kidneys of patients with idiopathic membranous nephropathy, while its predictive value has not been determined. It was a retrospective study, and 438 patients were included. Serum samples of two time points [before intervention (baseline) and after 1.5-year treatment (endpoint)] were detected for total and IgG4 anti-PLA₂R. IgG4 <0.26 RU/mL or total <20 RU/mL was considered as seronegativity. Bi-positivity/bi-negativity was defined when patients'antibodies were found positive or negative both at the baseline and endpoint. Completed remission (CR) was a major clinical outcome. A series of complement ingredients (MASP-1/2, MBL, C3a, C5a, Factor B, Ba, Bb and C5b-9) were measured in the patients of bi-positivity and bi-negativity: (1) meta-analysis based on six papers conducted seropositivity of anti-PLA₂R was a useful predictor for achieving CR, but there was a high heterogeneity; (2) there was significant correlation between the baseline and decrease in IgG4 subclass and the achievement of CR; (3) bi-negativity of IgG4 has a high accuracy of predicting CR compared with total antibodies; (4) in patients of bi-positivity, those achieving CR showed lower MASP-1/2, MBL, C3a, C5a, FB, Ba and Bb than patients failing to achieve CR; (5) the titers of endpoint and decrease in Ba and Bb were associated with improvement of 24 h-UP in those of bi-positivity; and (6) the decrease in Ba was a significant factor for achieving CR in those of bi-positivity. Continuous IgG4 negativity was a useful tool to predict the achievement of CR; however, in patients of continuous IgG4 positivity, those with lower activation of lectin and alternative pathways would still more probably achieve CR.