UNASSIGNED: Since the discovery of anti-neutrophil cytoplasmic autoantibodies (ANCA), great strides have been made in elucidating the etiology and pathogenesis of disease. In this article, we review recent published key breakthroughs in understanding the pathogenesis of ANCA @entity1333 , including some that may lead to novel therapeutics. These breakthroughs have occurred in multiple areas of investigation. A European genome-wide association study (GWAS) revealed the importance of the genetic contribution of @entity7134 ( @entity7134 ) and its endogenous inhibitor, alpha (1)-antitrypsin as well as HLA risk. Epigenetic modification of autoantigen genes appears to contribute to perpetuation of disease and possibly relapse risk. Autoantigen excision, a novel method to detect autoantibody epitopes using mass spectrometry, not only revealed pathogenic epitopes in @entity3335 ( @entity3335 )-ANCA @entity1333 and identified unique @entity3335 -ANCA responsible for the majority of @entity19417 , but has vast applicability to other autoantibody-mediated diseases. An explosion of biomarker studies has revealed circulating cytokines and alternative complement pathway products that may predict @entity66 . Interestingly, alternative complement pathway blockade in the @entity19 model of disease is protective and a clinical trial in @entity1 using an oral alternative complement pathway inhibitor is underway. Increasing clarity of the role of B and T cells in disease pathogenesis is ongoing. B cell depleting agents have shown great utility in remission induction and maintenance, and monitoring specific B cell subsets during the disease course may have predictive power for remission maintenance. Despite these substantial advances, more research is needed including, but not limited to, validation of existing discoveries. As additional novel discoveries emerge, so will novel therapies, and it is with great hope that these collective insights will ultimately lead to prevention and cure.

Recent pathogenetic advances in XXXX .

@entity1 :: ('9606', 'Species') :: ['humans'] @entity3335 :: ('4353', 'Gene') :: ['MPO', 'myeloperoxidase'] @entity66 :: ('MESH:D004194', 'Disease') :: ['active disease'] @entity1333 :: ('MESH:D014657', 'Disease') :: ['vasculitis'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity7134 :: ('5657', 'Gene') :: ['proteinase 3', 'PR3'] @entity19417 :: ('MESH:D056648', 'Disease') :: ['ANCA-negative small vessel vasculitis']
@entity19417 :: (MESH:D056648,Disease) :: ['ANCA-associated vasculitis']
