title: Cutting edge issues in Goodpasture's disease.
abstract: Goodpasture's disease, or anti-glomerular basement membrane (anti-GBM) disease, is a systemic autoimmune disorder defined by anti-GBM antibody-mediated damage (mainly immunoglobulin G-1) resulting in progressive crescentic glomerulonephritis and, frequently, diffuse pulmonary alveolar hemorrhage. It may be regarded as a "conformeropathy" where the quaternary structure of the α345NC1 hexamer that constitutes GBM undergoes a conformational change, exposing pathogenic epitopes on the α3 and α5 chains, eliciting a pathogenic autoantibody anti-GBM response. Goodpasture's disease accounts for 20% of all patients presenting with a pulmonary-renal syndrome and may be associated with detectable perinuclear antineutrophil cytoplasmic autoantibody positivity in up to a third of patients. Associated triggers may include tobacco smoking, hydrocarbon solvent exposure, and cocaine abuse. Cough, hemoptysis, and dyspnea with fatigue are the commonest presenting features. It is critical to rapidly distinguish Goodpasture's disease from other causes of pulmonary-renal syndromes such as Wegener's granulomatosis. Early and intensive treatment with plasmapheresis and immunosuppression with systemic corticosteroids pending results of diagnostic testing, and later cyclophosphamide, is often beneficial, with 90% of patients surviving the acute presentation of Goodpasture's disease. The need for hemodialysis on initial presentation, a serum creatinine >5 mg/dL, and 50% to 100% crescents on renal biopsy, portend the necessity of long-term hemodialysis. Further elucidation of the molecular pathobiology of Goodpasture's disease, particularly the regulation of involved antigen-specific T cells, may improve early diagnosis, treatment, and outcomes in this rare but potentially lethal autoimmune disorder.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, School of Medicine and VA Northern California Health Care System, University of California at Davis, Sacramento, USA. andrew.chan@ucdmc.ucdavis.edu
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Chan
authors.forename: Samuel
authors.initials: S
authors.lastname: Louie
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Leslie
authors.forename: Maya M
authors.initials: MM
authors.lastname: Juarez
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Albertson
mesh_terms: D000069594:Abatacept; D019867:Anti-Glomerular Basement Membrane Disease / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D001323:Autoantibodies / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D024141:Collagen Type IV / Q000276:immunology / Q000378:metabolism*; D003937:Diagnosis, Differential; D005260:Female; D005921:Glomerulonephritis; D006469:Hemoptysis; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000639:trends; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology*; D008875:Middle Aged; D010951:Plasma Exchange; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology*; D012307:Risk Factors; D012907:Smoking
chemical_list: D001323:Autoantibodies; D024141:Collagen Type IV; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept