title: Specificity of circulating and tissue-bound autoantibodies in Goodpasture syndrome.
abstract: Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.
authors.affiliation: Penn Center for Molecular Studies of Kidney Diseases, Department of Medicine, University of Pennsylvania, Philadelphia 19104-6144, USA.
authors.forename: R
authors.initials: R
authors.lastname: Kalluri
authors.forename: E
authors.initials: E
authors.lastname: Melendez
authors.forename: K W
authors.initials: KW
authors.lastname: Rumpf
authors.forename: K
authors.initials: K
authors.lastname: Sattler
authors.forename: G A
authors.initials: GA
authors.lastname: Müller
authors.forename: F
authors.initials: F
authors.lastname: Strutz
authors.forename: E G
authors.initials: EG
authors.lastname: Neilson
mesh_terms: D000293:Adolescent; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001665:Binding Sites; D003094:Collagen / Q000276:immunology*; D018604:Epitope Mapping; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C051951:antiglomerular basement membrane antibody; D003094:Collagen