Target antigens and antigen-specific clinical phenotypes in pediatric membranous nephropathy

Purpose: Primary membranous nephropathy (MN) is rare in childhood and increasingly understood as a spectrum of antigen- defined diseases. The distribution of glomerular target antigens and their clinical relevance in pediatric MN remain poorly defined.Methods: We systematically reviewed English-language reports of biopsy-confirmed MN diagnosed at ≤18 years of age. Databases were searched through August 1, 2026. Tissue-antigen and serum-antibody evidence were analyzed separately, overlapping cohorts were audited, and tissue M-type phospholipase A2 receptor (PLA2R) prevalence was pooled with a binomial-normal random- effects generalized linear mixed model.Results: Twenty-three reports were included. Ten independent tissue cohorts comprised 196 patients; 74 were PLA2R-positive (crude proportion, 37.8%). Pooled tissue PLA2R prevalence was 38.5% (95% confidence interval, 25.7%–53.2%; 95% prediction interval, 8.2%–81.5%; model-based I2=70.1%). Several cohorts suggested greater PLA2R positivity in older children. Exostosin 1 and 2 were linked to autoimmune or lupus-like features. All seven neural epidermal growth factor-like 1–positive patients were female and associated with environmental exposure. Semaphorin 3B positivity suggested early-childhood onset and male predominance.Conclusions: Current evidence is insufficient to use antigen status alone for prognostic or treatment stratification in pediatric MN. Nevertheless, antigen typing may refine diagnosis and etiologic evaluation by prompting assessment for autoimmunity or relevant exposures. Serial anti-PLA2R measurement may support patient monitoring although tissue and serum findings are not interchangeable.