Regulation of autoantibody responses to glomerular basement membrane in man and experimental animals.
Autoantibodies reacting with the glomerular basement membrane (GBM) are a rare cause of severe nephritis in man. Their development is HLA-DR-associated and their pathogenicity has been demonstrated by transfer experiments. Their production is spontaneously self-limiting over a period of years but irreversible renal failure usually occurs within weeks or months in the untreated patient. A regimen of intensive plasma exchange together with cytotoxic drugs and steroids induces a rapid and permanent arrest of antibody synthesis; this is associated with recovery of renal function, provided that target organ injury is not irreversible when treatment is initiated. To understand the homeostatic mechanisms engaged by the therapeutic regimen we have studied an experimental model of autoimmune nephritis in the Brown Norway rat, where autoantibody-mediated injury to the GBM is induced by mercuric chloride. Suppressor cells and humoral factors (putatively anti-idiotypic antibodies) were found to regulate autoantibody production, and cyclophosphamide can prevent its reinduction. To identify the autoantigenic component in human GBM we have produced a mouse monoclonal antibody which recognizes the same components as are recognized by autoantibodies from all 35 patients tested. This monoclonal antibody can be used to study the autoregulatory components from human blood which we have found to be important in the animal model.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology; D009393:Nephritis / Q000276:immunology; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D003520:Cyclophosphamide