Goodpasture Syndrome (Anti-GBM disease)

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. 

Microscopic polyangiitis (MPA) has an estimated incidence of approximately 0.5 to 1.8 cases per million per year. It demonstrates a bimodal age distribution, with peaks occurring between 20–30 years and again between 60–70 years. There is a male predominance. Genetic associations include HLA-DR15 and HLA-DR4, and environmental triggers such as smoking and hydrocarbon exposure have also been implicated in disease development.

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
• 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

Aetiology and Risk Factors

Aetiology: Autoantibodies directed against the non-collagenous (NC-1) domain of α3 chain of type IV collagen in lung and kidney basement membranes

Risk factors

• Genetic predisposition: HLA-DR15, HLA-DR4, HLA-DRB1*1501/1502 
• 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].

Pathophysiology

• Environmental insult (e.g. smoking) → alveolar capillary injury and increased antigen exposure.
• Autoimmune response: B cells produce anti-GBM antibodies targeting α3-NC1 type IV collagen
• Circulating antibodies bind linear epitopes in GBM and alveolar BM → complement activation → neutrophil-mediated inflammation and capillaritis
• Tissue damage: crescentic glomerulonephritis in kidneys; diffuse alveolar hemorrhage in lungs 

Clinical Manifestations

• Constitutional: fatigue, malaise, fever, weight loss, arthralgias
• Pulmonary: hemoptysis (may be absent), dyspnea, cough, chest pain (<50%), respiratory distress; crackles, cyanosis
• Renal: hematuria, proteinuria, oliguria, edema, hypertension, rapidly progressive renal failure (RPGN)
• Frequency: 60–80% dual involvement; 20–40% renal-only; <10% lung-only

Diagnosis

• Anti-GBM antibody
• Renal biopsy: crescentic GN, linear IgG deposition on GBM by immunofluorescence 
• ANCA (≈20–35% double positive)
• Complement levels; exclude other vasculitides or lupus

Differential diagnoses

• ANCA-associated vasculitis (e.g., GPA)—distinguished by presence of ANCA and pauci-immune GN
• SLE
• Other pulmonary hemorrhage causes (coagulopathy, infection)

Treatment

• Plasmapheresis: rapid removal of circulating anti-GBM antibodies
• High-dose corticosteroids plus cyclophosphamide or rituximab
• Azathioprine for maintenance 

Supportive care: dialysis for renal failure; respiratory support or intubation for pulmonary hemorrhage

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

References

1. Lee JY, et al. Goodpasture Syndrome. MSD Manual Professional. 2023.
   
2. Hellmark T, Segelmark M. Diagnosis and classification of Goodpasture’s disease. Div Nephrol. 2014.
   
3. Li T, McAdoo SP. Anti-GBM disease. BMJ Best Practice. 2024.
   
4. Kathuria P, Batuman V. Goodpasture Syndrome. Medscape. 2023.
   
5. Longo L, Martellucci S, Fusconi M. Goodpasture’s syndrome: a clinical update. Autoimmun Rev. 2015.
   
6. Wikipedia contributors. Goodpasture syndrome. Accessed 2025.