Goodpasture's Syndrome: An Autoimmune Conformational Disease

Abstract

Goodpasture's disease is an organ specific autoimmune disorder characterized by rapidly progressive glomerulonephritis with linear deposits of antibodies along the glomerular basement membrane and pulmonary hemorrhage induced by antibody binding to lung basement membranes. The disease has an incidence of 0.5 to 1.8 cases per million each year in Europian whites and Asian population. The disease predominantly affects white population with bimodial age distribution in 20 to 30 years and 60 to 70 years. Prevalence is higher in men in younger age group and women in older age sub group. The disease is thought to result from an environmental insult in a person with genetic susceptibility. The auto-antibodies bind to intrinsic antigens homogeneously distributed along the entire length of the glomerular basement membrane and activate complement, leading to inflammation and injury. Antibodies cross react with basement membrane in the lung alveoli producing simultaneous lung and kidney lesions. Typical clinical presentation consist of a combination of renal and pulmonary insufficiency. In patients with renal and pulmonary involvement biopsy should be considered to identify the underlying cause. Serological assays, light microscopy, immunofluorescence and electron microscopyis used to confirm diagnosis. Plasmapheresis and immunosuppressive therapy are commonly used treatment options. A combination therapy including Plasmapheresis, Corticosteroids and Cyclophosphamide has reduced mortality to 20%. The disease has poor prognosis inspite of treatment with mortality of 11% and high morbidity. The recent evidence suggesting the mechanism of conformational transition in Goodpature's antigen and the specificity of the autoantibody binding will pave the way for future research to elucidate the complete mechanism including identification of actual triggering factor and its activation, conformation of Goodpasture's autoantigens and the three dimensional structure of epitopes leading to development of new treatment options that can produce successful cure rates.