Goodpasture's disease: a report of ten cases and a review of the literature.

This review is based on our experience with ten patients diagnosed with Goodpasture's disease (GD). Six of the patients presented with combined renal and pulmonary insufficiencies; in the remaining four patients the clinical findings were limited to renal involvement. Circulating anti-glomerular basement membrane (GBM) autoantibodies were detected at diagnosis in all patients. Two patients were double-positive for anti-GBM and anti-proteinase-3 neutrophil cytoplasmic antibodies (c-ANCA). Another patient was double positive for anti-GBM and anti-myeloperoxidase cytoplasmic antibodies (p-ANCA). Four patients with rapidly progressive glomerulonephritis underwent hemodialysis: two of these patients died 6 and 8months after diagnosis, and the other two required maintenance dialysis. The remaining six patients were administered variable combinations of plasma-exchange, corticosteroids, and immunosuppressive drugs, which resulted in a remarkable and progressive improvement in renal function and one-year renal survival in all of them. Building on these observations, we provide an update on this relatively rare, frequently severe, and sometimes lethal autoimmune disease of unknown etiology. GD patients typically present with rapidly progressive renal insufficiency and pulmonary hemorrhage. Involvement restricted to the kidneys alone, as in our series, is also seen. The unfailing immunological hallmark of the disease is the occurrence of circulating anti-GBM antibodies, whose titer is directly related to the clinical severity of GD. The antibodies are associated with serum ANCAs in 10% to almost 40% of GD patients, with double positivity indicative of a worse renal prognosis. The target antigen of anti-GBM antibodies is a component of the non-collagenous-1 (NC1) domain of the α3 chain of type IV collagen, α345NC1. The prevalent expression of this hexamer on the basement membrane of both the glomeruli and the pulmonary alveoli accounts for the frequently combined renal and pulmonary involvement. A strong positive association of GD with the HLA-DRB1*15:01 allele has been described, but the factor(s) responsible for the loss of self-tolerance to NC1 autoantigen has not yet been identified. A conformational change in the quaternary structure of the α345NC1 likely plays a crucial role in triggering an immune response and justifies the proposed description of GD as an autoimmune "conformeropathy." The function of autoreactive T-cells in GD is poorly defined but may involve a shift from TH2 to TH1 cytokine regulation, such that affinity maturation and the antigen specificity of the antibody response are enhanced. The timely diagnosis of GD and the adoption of a triple therapeutic regimen comprising plasmapheresis, corticosteroids, and immunosuppressive drugs have remarkably improved the previously dismal outcome of these patients, resulting in a one-year survival rate of 70-90%.