Identification of the alpha 3 chain of type IV collagen as the common autoantigen in antibasement membrane disease and Goodpasture syndrome.
Antiglomerular basement membrane (GBM) antibodies can cause glomerulonephritis or pulmonary hemorrhage by themselves or Goodpasture syndrome when they occur together. It is unknown if variations in antibody reactivity contribute to the different patterns of organ involvement seen in this disease. This study examines the reactivity of the alpha 1-alpha 6 NC1 domains of Type IV collagen, the putative autoantigen, in sera from patients with anti-GBM antibodies after various clinical presentations of lung hemorrhage and renal injury. Serum or plasma containing anti-GBM antibodies from 35 patients with combined glomerulonephritis and pulmonary hemorrhage, 19 with glomerulonephritis alone, and 4 with pulmonary hemorrhage alone were compared with samples from 19 normal controls and 32 patients with other kidney diseases. Four different immunologic assays were performed with bovine alpha 1-alpha 6(IV) and recombinant human type alpha 1-alpha 5(IV) collagen NC1 domains. The study found that the anti-GBM antibodies from all patients reacted with the alpha 3(IV) NC1 (85% exclusively). Additional limited reactivity with the alpha 1(IV) NC1 and alpha 4(IV) NC1 was found in 15 and 3%, respectively. This non-alpha 3(IV) NC1 reactivity was most frequent in the patients with anti-GBM antibodies and glomerulonephritis alone. None of the patients had reactivity to other basement membrane components like laminin, fibronectin, heparan sulfate proteoglycan, entactin, or the 7S and triple helical fragments of Type IV collagen. The observed alpha-chain NC1 reactivity was confined to patients with anti-GBM antibodies with no additional reactivities detected among a large number of other kidney diseases controls. The correlation of alpha 1-alpha 6(IV) NC1 reactivity in a large number of patients with anti-GBM antibodies defined by classic assays definitively establishes that reactivity to alpha 3(IV) NC1 domains is both sufficient and necessary for the expression of autoimmune disease directed to the NC1 domain of Type IV collagen. On the basis of the evidence, the classification of antibasement membrane disease and Goodpasture syndrome as anti-Type IV collagen disease is proposed.
Kalluri
R
R
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center Kansas City, KS 66160, USA.
Wilson
C B
CB
Weber
M
M
Gunwar
S
S
Chonko
A M
AM
Neilson
E G
EG
Hudson
B G
BG
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology*; D002417:Cattle; D003094:Collagen / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology; D007678:Kidney Glomerulus / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology; D008297:Male; D011994:Recombinant Proteins
D001324:Autoantigens; D011994:Recombinant Proteins; D003094:Collagen