Membranous Glomerulonephritis (Primary and Secondary) • • • BM thickening Highly decreased cellular proliferation or infiltration Primary in adults (idiopathic) o Due to autoantibodies against phospholipase A2 receptor (PLA2R) found on podocytes • Secondary in children o Due to Hep B antigenaemia, autoimmune disorders, thyroiditis, carcinoma, gold, penicillamine, captopril and NSAIDs o Associated with mesangial/subendothelial deposits • Electron-dense deposits on EM subepithelium and intramembranously Tubular BM staining for IgG on IF is rare in primary but common in secondary forms such as lupus • • IgG deposits in primary are predominantly IgG4 whereas other isotypes have been found in secondary Pathogenesis 1. Antibodies target endocytic receptor megalin (gp300) on foot processes 2. Subepithelial immune deposits activate complement 3. 4. 5. 6. C5b-9 membrane attack complex forms It inserts into podocyte plasma membrane Complement-mediated podocyte injury follows This leads to proteinuria via the activation of signalling pathways in the podocyte that results in redistribution of actin and loss of slit diaphragm integrity. It also leads to GBM expansion by overproduction of type 4 collagen and laminin by injured podocyte PLA2R • • • • Phospholipase A2 receptor 80% idiopathic/primary membranous GN Blood tests available Predicts treatment response and prognosis THSD7A • Thrombospondin Type-1 Domain -Containing 7A • 10% idiopathic/primary