What is Goodpasture syndrome (Anti-Glomerular Basement Membrane disease)?

From the Guidelines

Goodpasture syndrome, also known as Anti-Glomerular Basement Membrane (Anti-GBM) disease, is a rare autoimmune disorder characterized by the presence of autoantibodies against the glomerular and alveolar basement membranes.

Key Characteristics

• It is a cause of small vessel vasculitis, presenting as a pulmonary-renal syndrome or renal-limited disease 1.
• The disease is caused by antibodies directed against the α3 chain of type IV collagen in the glomerular and alveolar basement membranes 1.
• If left untreated, it can lead to kidney failure and has a high mortality rate of up to 96% 1.

Diagnosis and Treatment

• Early diagnosis and treatment are crucial to prevent kidney failure and reduce mortality 1, 1.
• The recommended treatment includes immunosuppression with cyclophosphamide, glucocorticoids, and plasmapheresis 1, 1, 1.
• However, in patients who are dialysis-dependent at presentation, have 100% crescents or more than 50% global glomerulosclerosis, and do not have pulmonary hemorrhage, the risks and benefits of treatment should be carefully considered due to the poor prognosis 1, 1, 1.

From the Research

Definition and Characteristics

• Goodpasture syndrome, also known as Anti-Glomerular Basement Membrane (Anti-GBM) disease, is a rare and organ-specific autoimmune disease characterized by the presence of anti-GBM antibodies 2, 3, 4, 5, 6.
• The disease is mediated by autoantibodies against the NC1 domain of the alpha 3 chain of type IV collagen, leading to crescentic glomerulonephritis and linear immunofluorescent staining for IgG on the GBM 2, 3, 4.
• It typically presents as acute renal failure caused by a rapidly progressive glomerulonephritis, accompanied by pulmonary hemorrhage that may be life-threatening 2, 4, 5.

Pathophysiology and Etiology

• The etiology of Goodpasture syndrome is unknown, but researchers have hypothesized a genetic predisposition associated with HLA-DRB1()1501 and DRB1()1502 2, 6.
• Complex immunological mechanisms are involved in the pathogenesis of the disease, including the activation of the complement cascade and a type II hypersensitivity reaction 4, 6.
• The limited presence of the alpha 3 chain of type IV collagen in the body explains the disease's confinement to specific target organs, such as the lung and kidney 2, 3.

Clinical Presentation and Diagnosis

• The disease can present with rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage, and the presence of circulating autoantibodies to the GBM 2, 3, 4, 5.
• Diagnosis relies on the detection of anti-GBM antibodies in conjunction with glomerulonephritis and/or alveolitis 3, 6.
• Clinical symptoms can include renal failure, hematuria, proteinuria, and hemoptysis, and prompt diagnosis and treatment are vital for patients 2, 4, 5.

Treatment and Prognosis

• Treatment typically involves the use of glucocorticoids, cyclophosphamide, and plasma exchange therapy, with the goal of rapidly removing circulating autoantibodies and suppressing the immune system 4, 5.
• The prognosis for patients with Goodpasture syndrome is generally poor, with less than one third of patients surviving with preserved kidney function after 6 months of follow-up 6.
• Early diagnosis and treatment are essential for improving outcomes, and multi-centre international collaboration is required to provide insight into this disease and improve treatment options 5.