Overview
Goodpasture syndrome, now more precisely termed anti-glomerular basement membrane (anti-GBM) disease, is a rare autoimmune small-vessel vasculitis affecting lungs and kidneys, typically manifesting with diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis. Epidemiology: incidence approx. 0.5–1.8 cases per million per year; bimodal age peaks at 20–30 years and 60–70 years; male predominance; associations with HLA-DR15/DR4 and environmental triggers such as smoking and hydrocarbon exposure [8,4,1].
Definition
Anti-GBM disease: autoimmune condition where antibodies target the α3-NC1 domain of type IV collagen in glomerular and alveolar basement membranes [2,8].
Pulmonary-renal syndrome: simultaneous involvement of lungs (hemorrhage) and kidneys (glomerulonephritis).
Rapidly progressive glomerulonephritis (RPGN): rapid loss of kidney function often with crescents on biopsy, can be manifestation of anti-GBM disease.
Type II hypersensitivity: immune reaction where antibodies bind antigens on tissues, causing complement fixation and inflammation (mechanism here) [14].
Anatomy and Physiology
Relevant normal anatomy/physiology without disease:
• Glomerular basement membrane (GBM): multilaminar basal lamina between endothelial cells and podocytes—critical filtration barrier in kidney glomerulus [27].
• Alveolar basement membrane: part of the thin blood-air barrier for gas exchange in alveoli, consisting of alveolar epithelial and capillary endothelial layers plus basement membranes [26].
Aetiology and Risk Factors
Aetiology (cause):
• Autoantibodies directed against the non-collagenous (NC-1) domain of α3 chain of type IV collagen in lung and kidney basement membranes [1,4,11].
Risk factors:
• Genetic predisposition: HLA-DR15, HLA-DR4, HLA-DRB1*1501/1502 [1,2].
• Environmental triggers: cigarette smoking, hydrocarbon/organic solvent inhalation, viral respiratory infection (e.g., influenza) [1,8,4].
• Others: exposure to certain chemicals, infections, possibly post-renal transplant in Alport syndrome, heavy metals [4,8].
Remember
Genetic predisposition creates susceptibility—but environmental “hits” often precipitate disease.
Pathophysiology
Chronological ordering:
• Environmental insult (e.g. smoking) → alveolar capillary injury and increased antigen exposure [1].
• Autoimmune response: B cells produce anti-GBM antibodies targeting α3-NC1 type IV collagen [8,11].
• Circulating antibodies bind linear epitopes in GBM and alveolar BM → complement activation → neutrophil-mediated inflammation and capillaritis [1,2,8].
• Tissue damage: crescentic glomerulonephritis in kidneys; diffuse alveolar hemorrhage in lungs [7,14].
Think
Early damage to barrier exposes hidden antigens, tipping into autoimmune cascade.
Clinical Manifestations
• Constitutional: fatigue, malaise, fever, weight loss, arthralgias [8].
• Pulmonary: hemoptysis (may be absent), dyspnea, cough, chest pain (<50%), respiratory distress; crackles, cyanosis [8,1].
• Renal: hematuria, proteinuria, oliguria, edema, hypertension, rapidly progressive renal failure (RPGN) [8].
• Frequency: 60–80% dual involvement; 20–40% renal-only; <10% lung-only [8].
Triad: hemoptysis + glomerulonephritis + anti-GBM antibodies — diagnostic triad of Goodpasture syndrome.
Remember
Absence of hemoptysis does NOT rule out pulmonary involvement.
Diagnosis
Key investigations:
• Serology: anti-GBM antibody titre (ELISA for α3-NC1) [8,4].
• Renal biopsy: crescentic GN, linear IgG deposition on GBM by immunofluorescence [7].
• Additional: ANCA (≈20–35% double positive); complement levels; exclude other vasculitides or lupus [2,4].
Differential diagnoses: ANCA-associated vasculitis (e.g., GPA)—distinguished by presence of ANCA and pauci-immune GN; SLE—ANA, other autoantibodies; other pulmonary hemorrhage causes (coagulopathy, infection) [14].
Classification (Disease classification, not diagnosis):
• Within Chapel Hill Classification—anti-GBM disease classified as small-vessel vasculitis with in situ immune complex formation [2].
Treatment
• Plasmapheresis: rapid removal of circulating anti-GBM antibodies [5,4].
• Immunosuppression: high-dose corticosteroids plus cyclophosphamide; alternatives: rituximab, azathioprine for maintenance [8].
• Supportive care: dialysis for renal failure; respiratory support or intubation for pulmonary hemorrhage [4].
• Trigger avoidance: smoking cessation, avoid solvents, manage infections [4].
Clinical pearl: dual positive ANCA/anti-GBM cases may require prolonged immunosuppression [6].
Complications and Prognosis
Complications:
• Renal failure requiring long-term dialysis or transplant.
• Recurrent pulmonary hemorrhage.
• Infections due to immunosuppression.
• Rare relapse.
Prognosis:
• With early treatment: 5-year survival ~80%, >80% overall initial survival [8,4].
• Without treatment: nearly universally fatal.
• Poor prognostic factors: dialysis dependence at presentation, high creatinine, extensive crescents, delayed treatment [2].
Remember
Early intervention markedly improves outcomes.
Summary Table
| Section | Key High-Yield Points |
| Aetiology | Anti-GBM antibodies against α3-NC1 collagen |
| Risk factors | HLA-DR15/DR4, smoking, solvent exposure |
| Pathophysiology | Linear IgG deposition, complement activation, capillaritis |
| Clinical triad | Hemoptysis, glomerulonephritis, positive anti-GBM |
References
- Lee JY, et al. Goodpasture Syndrome. MSD Manual Professional. 2023.
- Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture’s disease. Div Nephrol. 2014.
- Li T, McAdoo SP. Anti-GBM disease. BMJ Best Practice. 2024.
- Kathuria P, Batuman V. Goodpasture Syndrome. Medscape. 2023.
- Longo L, Martellucci S, Fusconi M. Goodpasture’s syndrome: a clinical update. Autoimmun Rev. 2015.
- Wikipedia contributors. Goodpasture syndrome. Accessed 2025.
Discussion