Anti-PLA2R IgG4-to-IgG Ratio Helps Predict Remission of PLA2R-Associated Primary Membranous Nephropathy

PLA2R-associated primary membranous nephropathy (PMN) was classified as IgG4-associated autoimmune disease, in which anti-PLA2R antibody is predominantly IgG4 subclass. Our objective was to explore the capability of anti-PLA2R IgG4-to-IgG ratio for predicting remission in PLA2R-associated PMN patients.

A total of 143 patients with anti-PLA2R IgG ≥14 RU/mL were biopsy-confirmed as PLA2R-associated PMN. Serum samples collected at the time of renal biopsy were tested for anti-PLA2R IgG and anti-PLA2R IgG4 using time-resolved fluoroimmunoassay. The anti-PLA2R IgG4-to-IgG ratio was calculated as anti-PLA2R IgG4 (ng/mL) divided by anti-PLA2R IgG (RU/mL). Patients were divided into high-ratio and low-ratio groups by cutoff value of 31.5 ng/RU determined by the maximally selected log-rank statistic. The relationship between anti-PLA2R IgG4-to-IgG ratio and remission was analyzed using Cox proportional hazard regression.

Compared to the low-ratio group, patients in the high-ratio group were significantly younger (52 [40-60] vs. 58 [51-61] years, p = 0.035), had higher estimated glomerular filtration rate (102 [88-111] vs. 94 [72-100] mL/min/1.73 m2, p = 0.004), and obtained higher 6-month partial remission rates (64.6% vs. 30.0%, p = 0.001) and 1-year complete remission rates (38.3% vs. 7.7%, p = 0.003). The higher remission rates with high ratio remained in both moderate-low-risk and high-risk subgroups categorized according to KDIGO 2021 guidelines. The anti-PLA2R IgG4-to-IgG ratio had a significant positive relation with partial remission (hazard ratio [95% confidence interval] = 2.09 [1.27-3.46], p = 0.004), which also persisted across both risk subgroups. Kaplan-Meier survival curves confirmed the significantly higher possibility of partial remission in the high-ratio group.

An elevated anti-PLA2R IgG4-to-IgG ratio may be a supplementary predictor for remission in PLA2R-associated PMN.