Suppression of experimental membranous glomerulonephritis in rats by an anti-MHC class II antibody

Background: We previously reported that idiopathic membranous nephropathy ( IMN) strongly correlated with HLA-DRB1*1501-DRB5*0101-DQAI*0102-DQB1*0602, a specific haplotype of human major histocompatibility complex (MHC), in Ja panese patients. To investigate the role of MHC in the development of rat H eymann nephritis (HN), an animal model of membranous nephropathy, a monoclo nal antibody (mAb) specific to rat MHC class II antigen (RT1B) was administ ered, and its effectiveness in inhibiting HN was assessed. Methods: Active HN was induced in HN-sensitive Lewis rats by administering brush border pro teins of rat proximal uriniferous tubules (FX1A). Rats were divided into fo ur groups: rats treated with 1,000 mug anti-rat MHC class II mAb, rats trea ted with 100 mug anti-rat MHC class II mAb, rats treated with murine myelom a IgG, and rats that did not receive either FX1A or any other mAb, We exami ned the differences in 24-hour urinary protein excretion and serum alloanti body titers against FX1A between groups at different time intervals, and th e histologic features of kidneys at the end of the study. Results: HN was i nduced in Lewis rats by inoculation with FX1A antigen. Administration of a nti-M HC class II mAb successfully lowered urinary proteins, production of anti-FX1A alloantibodies, and the development of glomerular lesions in a do se-dependent manner. Conclusion: The present results demonstrated that the MHC class II molecule itself is directly involved in the pathogenesis of HN , and suggest that this therapy would be any better (or less toxic) than no nselective immunosuppressants in the treatment of IMN, Copyright (C) 2001 S . Karger AG, Basel.