Anti-Glomerular Basement Membrane Disease (Goodpasture’s Syndrome)

Anti-glomerular basement membrane disease is a rare autoimmune disorder that primarily affects the kidneys and lungs. It is characterized by the development of autoantibodies against the non-collagenous domain of the α3 chain of type IV collagen, which is a critical component of the basement membranes in the kidneys and lungs. These autoantibodies can lead to inflammation and serious damage in these organs in the short term, with approximately 90% of patients having rapidly progressive glomerulonephritis, with or without lung hemorrhage. Patients with 100% crescents on kidney biopsy who require dialysis and show kidney failure at presentation have a dismal kidney survival rate of 8% at 1 year of follow-up. This makes anti-GBM disease one of the most aggressive forms of glomerulonephritis. Treatment is based on plasma exchange, which rapidly removes the pathogenic autoantibody, together with corticosteroids and cyclophosphamide, which inhibits autoantibody production and ameliorate inflammation. Despite treatment, currently the renal prognosis of patients who require dialysis at the time of diagnosis is poor. Imlifidase, an immunoglobulin G (IgG)-specific protease that cleaves human IgG into F(ab’)2 and Fc fragments, has been proposed as an alternative to plasma exchange in refractory forms of anti-GBM disease. If the promising results obtained with imlifidase are confirmed by the ongoing phase 3 trial (NCT05679401), a paradigm shift in the treatment of the disease will occur.