Anti-Glomerular Basement Membrane Glomerulonephritis
Anti-Glomerular Basement Membrane Glomerulonephritis
Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by IgG autoantibodies against the glomerular basement membrane. We describe clinical and pathologic findings in a series of renal biopsy specimens from 80 patients. The patients ranged in age from 16 to 87 years. The age distribution was bimodal, with one peak at a young age predominated by males and a second peak in the sixth to eighth decades with females predominating. Most patients (70 [88%]) had severe necrotizing glomerulonephritis with crescents in more that 50% of glomeruli. The fraction of crescentic glomeruli in biopsy specimens correlated well with serum creatinine levels but not with serologic titers for anti-GBM antibodies. Interstitial fibrosis was uncommon and, when present, minimal to mild. Linear IgG deposition defines this entity, but immunofluorescent costaining for other immunoglobulins and complement is found frequently. To our knowledge, this is the largest series of renal biopsy specimens with anti-GBM glomerulonephritis studied to date.
Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is an autoimmune disease that clinically manifests as a rapidly progressive glomerulonephritis. When accompanied by pulmonary hemorrhage, it is designated the Goodpasture syndrome. Anti-GBM glomerulonephritis is rare, with an incidence of 0.5 to 1 case per million per year in the United States. It leads to acute renal failure and progression to end-stage renal disease in most cases. However, earlier diagnosis and better supportive care dramatically improved patient survival during the past decades. Plasmapheresis and immunosuppressive drugs are the most important treatment strategies. Two parameters have emerged as reliable predictors of adverse outcome: the fraction of crescentic glomeruli in biopsy specimens and anuria or a serum creatinine level greater than 5 mg/dL (442 µmol/L) at diagnosis.
Anti-GBM glomerulonephritis is one of the few human autoimmune diseases in which the autoantigen has been identified. It is designated the Goodpasture antigen and comprises the noncollagenous domain (NC1) of the α-3 chain of type IV collagen. IgG autoantibodies against this antigen have been proven to be the pathogenetic agent, and linear IgG deposition along the GBM defines the disease. The deposited immunoglobulin is generally of the IgG1 class, although rare IgA-mediated cases have been described. In their seminal work, Lerner et al elucidated the pathogenetic role of anti-GBM antibodies in patients with glomerulonephritis by injecting eluates from kidney tissue into nonhuman primates. The authors were able to transfer the nephritis from patients to 2 monkeys, and severe proliferative glomerulonephritis developed in both monkeys. Kidneys from both monkeys showed linear basement membrane staining for IgG. The pathogenetic role of anti-GBM antibodies was substantiated further when the nephritis recurred in patients who had received renal allografts before elimination of the autoantibody from their serum.
Advances in our understanding of the molecular and immunologic mechanisms of the disease were reviewed recently. However, no large studies that focus on renal biopsy findings have been published recently. We reviewed the biopsy pathology of 80 patients diagnosed with anti-GBM glomerulonephritis.
Abstract and Introduction
Abstract
Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare disease caused by IgG autoantibodies against the glomerular basement membrane. We describe clinical and pathologic findings in a series of renal biopsy specimens from 80 patients. The patients ranged in age from 16 to 87 years. The age distribution was bimodal, with one peak at a young age predominated by males and a second peak in the sixth to eighth decades with females predominating. Most patients (70 [88%]) had severe necrotizing glomerulonephritis with crescents in more that 50% of glomeruli. The fraction of crescentic glomeruli in biopsy specimens correlated well with serum creatinine levels but not with serologic titers for anti-GBM antibodies. Interstitial fibrosis was uncommon and, when present, minimal to mild. Linear IgG deposition defines this entity, but immunofluorescent costaining for other immunoglobulins and complement is found frequently. To our knowledge, this is the largest series of renal biopsy specimens with anti-GBM glomerulonephritis studied to date.
Introduction
Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is an autoimmune disease that clinically manifests as a rapidly progressive glomerulonephritis. When accompanied by pulmonary hemorrhage, it is designated the Goodpasture syndrome. Anti-GBM glomerulonephritis is rare, with an incidence of 0.5 to 1 case per million per year in the United States. It leads to acute renal failure and progression to end-stage renal disease in most cases. However, earlier diagnosis and better supportive care dramatically improved patient survival during the past decades. Plasmapheresis and immunosuppressive drugs are the most important treatment strategies. Two parameters have emerged as reliable predictors of adverse outcome: the fraction of crescentic glomeruli in biopsy specimens and anuria or a serum creatinine level greater than 5 mg/dL (442 µmol/L) at diagnosis.
Anti-GBM glomerulonephritis is one of the few human autoimmune diseases in which the autoantigen has been identified. It is designated the Goodpasture antigen and comprises the noncollagenous domain (NC1) of the α-3 chain of type IV collagen. IgG autoantibodies against this antigen have been proven to be the pathogenetic agent, and linear IgG deposition along the GBM defines the disease. The deposited immunoglobulin is generally of the IgG1 class, although rare IgA-mediated cases have been described. In their seminal work, Lerner et al elucidated the pathogenetic role of anti-GBM antibodies in patients with glomerulonephritis by injecting eluates from kidney tissue into nonhuman primates. The authors were able to transfer the nephritis from patients to 2 monkeys, and severe proliferative glomerulonephritis developed in both monkeys. Kidneys from both monkeys showed linear basement membrane staining for IgG. The pathogenetic role of anti-GBM antibodies was substantiated further when the nephritis recurred in patients who had received renal allografts before elimination of the autoantibody from their serum.
Advances in our understanding of the molecular and immunologic mechanisms of the disease were reviewed recently. However, no large studies that focus on renal biopsy findings have been published recently. We reviewed the biopsy pathology of 80 patients diagnosed with anti-GBM glomerulonephritis.
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