Goodpasture syndrome: molecular and clinical advances.

Goodpasture syndrome is a rare but important autoimmune disorder characterized by pulmonary hemorrhage and glomerulonephritis. Typically striking young men, it is rapidly progressive and fatal unless treated early. Although the pathogenesis is largely unknown, recent investigations have established that antibodies are directed against the noncollagenous domain of the alpha 3 chain of type IV collagen. Differences in expression and exposure of this chain account for the tissue selectivity of the antibodies and the pulmonary and renal targets of clinical disease. Certain individuals appear at risk by virtue of HLA association, but why only some develop GS remains unclear. Intriguing observations suggest that cigarette smoking, infection, or chemicals expose the antigen, leading to antibody production in genetically susceptible individuals. Before plasmapheresis was available to remove antibodies, prognosis was bleak, and most patients died or were left with permanent renal impairment. Current combination therapy with plasmapheresis and immunosuppressive drugs is unlikely to be successful unless instituted early in appropriate patients. Fortunately, the autoimmune process is limited, as demonstrated by the small number of reported cases of recurrent disease.