A Target Antigen–Based Approach to the Classification of Membranous Nephropathy

ObjectiveTo describe the clinical and pathological phenotype of membranous nephropathy (MN) associated with M-type-phospholipase–A2-receptor (PLA2R), thrombospondin-type-1-domain-containing-7A (THSD7A), semaphorin 3B (SEMA3B), neural-epidermal-growth-factor-like-1-protein (NELL-1), protocadherin 7 (PCDH7), exostosin 1/exostosin 2 (EXT1/EXT2) neural cell adhesion molecule 1 (NCAM-1) as target antigens.MethodsA retrospective cohort 270 adult patients biopsy-proven MN diagnosed between January 2015 April 2020 was classified PLA2R-, THSD7A-, SEMA3B-, NELL-1–, PCDH7-, EXT1/EXT2-, NCAM-1–associated or septuple-negative using serologic tests, immunostaining, and/or mass spectrometry. Clinical, biochemical, pathologic, follow-up data were systematically abstracted from medical records, including disease activity conditions traditionally occurring within 5 years diagnosis.ResultsPatients PLA2R-associated predominantly middle-aged white men without disease. The presence did not affect pathologic characteristics MN, suggesting that they coincidental rather than causally linked. rare SEMA3B-associated discovered in our cohort. EXT1/EXT2-associated primarily younger women active systemic autoimmunity. A significant proportion had malignancy autoimmunity.ConclusionThe widely used distinction primary secondary has limitations. We propose a refined terminology combines antigen to better classify guide decision making.