Advances in human antiglomerular basement membrane disease

Antiglomerular basement membrane (anti-GBM) disease is an autoimmune disorder that mostly presents as raised titers of antibodies against the GBM, rapidly progressive glomerulonephritis and pulmonary hemorrhage. The disease is caused by antibodies against noncollagenous domain of α3 chain of type IV collagen, which contains the epitopes E(A) and E(B). The humoral and cellular immunity contributing to the initiation of anti-GBM disease has been extensively studied as a model for autoimmune diseases, although most of the data come from animal studies. The disease is rare, but diagnoses have been made in hundreds of patients. Substantial advances have been made in the understanding of human anti-GBM disease, and it can be treated successfully. In this Review we summarize the current knowledge on the prevalence, clinical manifestations, treatment and outcomes of human anti-GBM disease. We discuss findings on pathogenesis from human studies, with close attention to disease initiation and the immunological features of progression from quiescent autoimmune homeostasis in healthy individuals to fulminant anti-GBM disease. Further studies on autoreactive T cells are expected to clarify specific features of human anti-GBM disease and could lead to the development of new therapies.