An unusual case of pulmonary-renal syndrome associated with defects in type IV collagen composition and anti-glomerular basement membrane autoantibodies

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 α3NC1 domain), but against the α2NC1 domain of type IV collagen. Our findings represent the first known case of human autoantibodies to the α2NC1 domain. Further investigation showed that this patient has decreased α3 and α5 chain expression in the GBM and defects in type IV collagen, resembling abnormalities in patients with Alport's syndrome.