A Case of Pla2r and Exostosin 1 Positive Membranous Nephropathy - The Diagnostic and Therapeutic Dilemma

Membranous nephropathy is an immune disease that commonly presents as nephrotic syndrome. The understanding of the pathogenesis of membranous nephropathy has rapidly evolved over the past few years due to the discovery of newer antigens. Exostosin 1 and exostosin 2 are antigens discovered in 2019 and found to be specific for membranous nephropathy secondary to autoimmune disease and are usually not seen in M-type phospholipase A2-associated membranous nephropathy. However, fewer clinical and pathological details of exostosin 1 and 2 related nephropathies are known, owing to the novelty of the antigen. Here we report a 24-year-old female who presented with nephrotic range proteinuria. Initial blood investigations revealed a doubtful autoimmune disease background. A subsequent renal biopsy revealed membranous nephropathy with both PLA2r and exostosin 1 positivity, which posed challenges in both diagnosis and treatment. Immunoglobulin G staining and electron microscopy were performed to differentiate if it was a PLA2r-associated or a exostosin 1/ exostosin 2-related membranous nephropathy. Electron microscopy revealed subepithelial deposits and immunoglobulin G stained for immunoglobulin G4, signifying possible PLA2r-associated membranous nephropathy with exostosin deposits. The patient was treated with rituximab and had a good treatment response. Only one similar case has been reported with both PLA2R and exostosin positivity. The pathophysiologic mechanism of this unique association is still unclear.