FIGURE 1.

Mechanisms of formation of subepithelial immune complex deposits. The depositions of subepithelial immune complexes might form either in situ immune complexes or circulating immune complexes that contained circulating antibodies binding to endogenous antigens (megalin, NEP, PLA₂R, and THSD7A) in podocytes or to exogenous antigens (CBSA, hepatitis B antigen, and enzyme replacement therapy) planted in GBM. In total, four endogenous antigenic targets have been identified, including megalin in Heymann nephritis, NEP in alloimmune neonatal MN, and PLA₂R and THSD7A in IMN. In total, four circulating exogenous antibodies can target surface-exposed intrinsic podocyte antigens to cause capping and shedding of in situ antigen–antibody complex into underlying GBM. CBSA, enzyme from enzyme replacement therapy, and hepatitis B antigen may traverse GBM and bind under podocyte as planted antigens and also as target for circulating antibodies. In addition, circulating immune complexes deposited in the subepithelial region.