SPECIFICITY OF CIRCULATING AND TISSUE-BOUND AUTOANTIBODIES IN GOODPASTURE-SYNDROME

Goodpasture syndrome is an often fatal autoimmune disease associated w ith glomerulonephritis and/or pulmonary hemorrhage. The clinical manif estations of this disease correlate well with the presence of circulat ing antiglomerular basement membrane (GEM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thoug ht to be the alpha 3 chain of type IV collagen. Nearly all that is kno wn about anti-GBM antibodies in humans comes from work on unbound circ ulating antibody. We recently had the unique and rare opportunity to o btain early postmortem antibody and tissues from a patient who died wi th catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evalu ated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tiss ue-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 an d circulating antibodies compete with one another for overlapping epit opes on the antigen. These findings demonstrate that circulating autoa ntibodies in Goodpasture syndrome are highly representative of those b ound to organ tissues, strengthening the notion that pathogenic autoan tibodies are targeted to the alpha 3(TV)NC1 collagen, and that previou s reports of findings in the circulation may be applicable to tissue i njury.