Role of receptor-associated 39/45 kD protein in active Heymann nephritis

Active Heymann nephritis (HN) of rat, an autoimmune glomerular disease, is an experimental model of human membranous glomerulonephropathy (MGN), a common human glomerular disease. The putative autoantigen of HN is believed to be a large glycoprotein (gp330) present in kidneys of rat and human. Gp330 has sequence homology to low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor and co-purifies with another 45 kD protein called receptor-associated protein (RAP) which binds to both gp330 and LRP/alpha 2-macroglobulin receptor. Since RAP co-purifies with gp330 and is thus present in the immunizing material used to induce active HN, the present study was undertaken to determine if gp330 or RAP individually could produce active HN and whether RAP had a role in the pathogenesis of active HN. Rats immunized with the traditional crude antigen (Fx1A) containing both gp330 and RAP developed typical HN. Although these rats developed low titers of autoantibody to RAP in their sera, they had no deposition of antibody to RAP in their kidneys. Rats immunized with gp330 also developed typical HN but had no autoantibody to RAP in their sera or kidneys. Rats immunized with RAP developed high titers of autoantibody to RAP in their sera but had no antibody in their kidneys and did not develop HN. Three rats were injected intravenously with polyclonal antibody to RAP and assessed seven days later for the development of passive HN. All three developed mild passive HN characterized by granular staining of polyclonal antibody along the capillary loops.

(1) This is the first report to show that gp330 alone without the accompanying RAP can induce active HN; (2) RAP by itself does not induce active HN; (3) Autoantibodies to RAP do not appear to be involved in the pathogenesis of active HN induced with the traditional crude antigen, Fx1A; and (4) We confirm that polyclonal antibody to RAP can induce passive HN.