Patients with antineutrophil cytoplasmic antibody-associated vasculitis have defective Treg cell function exacerbated by the presence of a suppression-resistant effector cell population.

摘要: Objective The development of pathogenic antineutrophil cytoplasmic antibodies (ANCAs) can result in systemic small vessel vasculitis. However, the breakdown immune tolerance that results induction and persistence ANCAs is not well understood. We undertook this study to test our hypothesis abnormal T cell regulation central disease pathogenesis patients with ANCA-associated vasculitis (AAV). Methods Peripheral blood samples were obtained from 62 AAV 19 healthy controls for flow cytometric analysis CD4+ populations. Functional studies performed fluorescence-activated sorted populations stimulated anti-CD3/anti-CD28. Results We demonstrated two separate abnormalities AAV. First, we showed Treg frequency was increased peripheral active disease, but cells had decreased suppressive function. disproportionately used a FoxP3 isoform lacking exon 2, which might alter Second, identified population resistant suppression, produced proinflammatory cytokines, antigen experienced. Conclusion AAV associated disruption network distinct effector subset comprises majority cells.