From the Guidelines
Goodpasture syndrome, also known as Anti-GBM disease, is a rare autoimmune disorder characterized by the production of antibodies against the alpha-3 chain of type IV collagen in the basement membranes of lung and kidney tissues, leading to inflammation and damage. This condition typically presents as a pulmonary-renal syndrome, with symptoms including coughing up blood, difficulty breathing, fatigue, and signs of kidney damage such as blood and protein in urine, high blood pressure, and potentially kidney failure 1. The disease is most often caused by antibodies directed against an intrinsic antigen in the noncollagenous (NC1) domain of the α3 chain of type IV collagen, which is present in the glomerular and alveolar basement membranes 1.
Key Characteristics
- The immune system mistakenly attacks the lungs and kidneys
- Antibodies are produced against the alpha-3 chain of type IV collagen
- Inflammation and damage to lung and kidney tissues occur
- Symptoms include coughing up blood, difficulty breathing, fatigue, and signs of kidney damage
Treatment
Treatment typically involves immunosuppressive medications such as cyclophosphamide and glucocorticoids, plus plasmapheresis in all patients with anti-GBM GN, except those who are treated with dialysis at presentation, have 100% crescents or > 50% global glomerulosclerosis in an adequate biopsy sample, and do not have pulmonary hemorrhage 1. Plasmapheresis should be continued until the anti-GBM antibody levels are negative on 2 consecutive tests, as most cases (97%) have undetectable anti-GBM antibodies within 8 weeks of immunosuppression and plasma exchange initiation 1. Early diagnosis and aggressive treatment are crucial, as the condition can progress rapidly and cause permanent organ damage, with a mortality rate of up to 96% in untreated patients 1.
From the Research
Definition and Pathology
- Goodpasture syndrome, also known as Anti-GBM disease, is a rare autoimmune disease characterized by the presence of anti-glomerular basement membrane (anti-GBM) antibodies 2, 3, 4.
- The disease is mediated by these antibodies, which target the noncollagenous domain of the alpha 3 chain of type IV collagen, leading to crescentic glomerulonephritis and linear immunofluorescent staining for IgG on the glomerular basement membrane 4, 5.
- The pathology of Goodpasture syndrome is characterized by renal and pulmonary manifestations, including glomerular crescent formation, linear immunofluorescent staining, and alveolar infiltration and hemorrhage 2, 3.
Clinical Presentation
- Goodpasture syndrome typically presents as acute renal failure caused by rapidly progressive glomerulonephritis, accompanied by pulmonary hemorrhage, which may be life-threatening 4, 5.
- Patients may also experience symptoms such as hemoptysis, dyspnea, cough, and fatigue 2, 3.
- In some cases, the disease may present with atypical features, such as seronegativity for anti-GBM antibodies and nephrotic-range proteinuria 2, 3.
Diagnosis and Treatment
- Diagnosis of Goodpasture syndrome is often based on a combination of clinical presentation, laboratory tests, and renal biopsy 2, 3, 4.
- Treatment typically involves immunosuppressive therapy, including plasma exchange, prednisolone, and cyclophosphamide, to remove antibodies and suppress the immune system 6, 5.
- Early aggressive therapy is essential to improve prognosis and maximize the chance of renal recovery 6, 5.
Prognosis and Outcome
- The prognosis of Goodpasture syndrome depends on the severity of renal failure and the promptness of treatment 6.
- Patients who present with severe renal failure are less likely to recover renal function, and those who require immediate dialysis are less likely to recover 6.
- With current combination therapy, patient and renal survival rates have improved, but the disease remains a significant challenge due to its rarity and complexity 6, 5.