Molecular Mechanisms of In Situ Immune Complex Formation in Experimental Membranous Nephropathy

Membranous glomerulopathy (MGN) is characterized by the deposition of granular immune complexes in the glomerular basement membrane (GBM) that corresponds to subepithelial dense immune deposits in the lamina rara externa seen by electron microscopy1. The progression of this disease to renal insufficiency is not influenced in a significant number of cases, despite aggressive immunosuppressive therapies.2–4 Therefore, a specific therapy for MGN is needed which can be only conceived when its pathogenic mechanisms are understood. This requires: (1) the identification of molecule(s) which serve as the antigen(s) in the initial immune complexes; (2) the precise analysis of the mechanisms of stablization and growth of the nascent antibody-antigen complexes to permanent subepithelial immune deposits; and (3) clarification of the secondary mechanisms which trigger complex pathophysiological reactions in the glomerulus.