title: Advances in the pathogenesis of Goodpasture's disease: from epitopes to autoantibodies to effector T cells.
abstract: Goodpasture's disease, an "organ-specific" autoimmune disease is manifest by rapidly progressive glomerulonephritis and pulmonary hemorrhage. Studies into the pathogenesis of this disease have shed light on the autoantigen (the non-collagenous domain of the alpha3 chain of type IV collagen, alpha3(IV)NC1) and its epitopes, as well as the involvement of autoantibodies and cellular effectors in disease. The discovery of alpha3(IV)NC1 lead to studies that defined the structure and biology of type IV collagen and are defining B and T cell epitopes. Goodpasture autoantibody epitopes are "cryptic" in that they are structurally sequestered by adjacent non-collagenous domains of alpha4 and alpha5 type IV collagen. T cell epitope studies in rats demonstrated that a 13-mer could induce experimental autoimmune glomerulonephritis. T cells from patients with Goodpasture's recognize two epitopes, in regions which are highly susceptible in antigen processing by endosomal proteases. Goodpasture's disease is strongly associated with HLA DRB1 genes, whereby DRB1*1501 confers susceptibility and the DRB1*0701 and DRB1*0101 are dominantly protective. Experimental data implicate both autoantibodies and cell mediated immunity as disease effectors. Observations in humans suggest that regulatory T cells are associated with the development of self-immunoregulation in the convalescent phase of disease.
authors.affiliation: Monash University Department of Medicine, Monash Medical Centre, Clayton, VIC 3168, Australia.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Ooi
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology* / Q000378:metabolism; D024141:Collagen Type IV / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D018984:Epitopes, T-Lymphocyte; C057112:type IV collagen alpha3 chain