title: An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies.
abstract: Commercial serological assays for the presence of anti-glomerular basement membrane (GBM) antibodies are thought to be indicative of Goodpasture's syndrome. We report a case in which commercial tests inaccurately suggested that a patient with a pulmonary-renal syndrome had Goodpasture's disease. Additional laboratory testing using recombinant type IV collagen NC1 domain proteins showed that the autoantibodies in question were not directed against the Goodpasture antigen (the alpha3NC1 domain), but against the alpha2NC1 domain of type IV collagen. Our findings represent the first known case of human autoantibodies to the alpha2NC1 domain. Further investigation showed that this patient has decreased alpha3 and alpha5 chain expression in the GBM and defects in type IV collagen, resembling abnormalities in patients with Alport's syndrome.
authors.affiliation: Department of Medicine, Center for Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA 02215, USA.
authors.forename: David
authors.initials: D
authors.lastname: Charytan
authors.forename: Brian
authors.initials: B
authors.lastname: MacDonald
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Stephen
authors.initials: S
authors.lastname: Pastan
authors.forename: Gerald
authors.initials: G
authors.lastname: Staton
authors.forename: Randy
authors.initials: R
authors.lastname: Hennigar
authors.forename: Raghu
authors.initials: R
authors.lastname: Kalluri
mesh_terms: D000328:Adult; D019867:Anti-Glomerular Basement Membrane Disease / Q000175:diagnosis*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology*; D015153:Blotting, Western; D024141:Collagen Type IV / Q000737:chemistry / Q000276:immunology*; D003951:Diagnostic Errors; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D008297:Male; D009394:Nephritis, Hereditary / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013577:Syndrome
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D011993:Recombinant Fusion Proteins; C057112:type IV collagen alpha3 chain