Advances in the genetics of anti-glomerular basement membrane disease

Anti-glomerular basement membrane (GBM) disease is a rare but lethal autoimmune disorder. Over the past few years, the nature of the autoantigen and its epitopes has been defined, as well as the possible pathogenic role played by environmental factors, and by cellular and humoral immunity. However, the majority of data on anti-GBM disease comes from studies conducted on animal models, since human studies are relatively scarce. Genetic studies have highlighted strong positive associations of anti-GBM disease with the HLA-DRB1*1501 allele. In addition, the disease has been associated with genes of the FCGR and KLK families. Important as they are, these findings have to be considered preliminary, if not contentious. Here, we provide an overview of recent discoveries in the genetics of anti-GBM disease that may help elucidate the disease pathogenesis while improving therapeutic approaches. We also discuss the limitations of such discoveries. Finally, we suggest that extensive collaboration between investigators and novel integrative approaches are essential to the progress of our understanding of the anti-GBM disease. We attempted to summarize the current knowledge on the pathogenesis of anti-GBM disease by providing different but complementary perspectives from previous reviews.