Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands; Department of Nephrology, University Duisburg-Essen, Essen, Germany.
Department of Internal Medicine, Division of Clinical and Experimental Immunology, University Hospital Maastricht, Maastricht, The Netherlands.
Kidney Int. 2011 Mar;79(6):599-612. doi: 10.1038/ki.2010.472. Epub 2010 Dec 8.
ANCA-associated-vasculitis (AAV) comprises three different diseases entities: Churg-Strauss syndrome, microscopic polyangiitis, and Wegener's granulomatosis. AAV is an autoimmune disease with complex pathophysiology. Anti-neutrophil cytoplasmic antibodies (ANCAs) with specificity for proteinase-3 (PR3) or myeloperoxidase (MPO) are hallmarks of AAV and have a pivotal role in disease development. In addition to ANCA, the cellular immune system contributes to the pathogenesis of the disease. ANCA-mediated degranulation of neutrophils causes vasculitic damage; T cells drive granuloma formation, promote vasculitic damage by several different pathways, and enhance autoantibody production by B cells. Recently, complementary PR3 and lysosomal membrane protein-2 were suggested as novel autoantigens in AAV. New findings also indicate the importance of complement, danger-associated molecular patterns, and dendritic cells in AAV. This review highlights novel pathophysiological findings in AAV and puts them into context with the current understanding of disease mechanisms. Furthermore, implications for present and new therapeutic strategies are discussed.
抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）包括三种不同的疾病实体：Churg-Strauss 综合征、显微镜下多血管炎和韦格纳肉芽肿。AAV 是一种具有复杂病理生理学的自身免疫性疾病。抗中性粒细胞胞浆抗体（ANCA）特异性针对蛋白酶 3（PR3）或髓过氧化物酶（MPO），是 AAV 的标志，在疾病发展中起关键作用。除了 ANCA，细胞免疫系统也有助于疾病的发病机制。ANCA 介导的中性粒细胞脱颗粒导致血管炎损伤；T 细胞通过多种不同途径驱动肉芽肿形成，促进血管炎损伤，并增强 B 细胞产生自身抗体。最近，补充 PR3 和溶酶体膜蛋白-2 被认为是 AAV 的新自身抗原。新的发现也表明补体、危险相关分子模式和树突状细胞在 AAV 中的重要性。本综述强调了 AAV 中新型病理生理学发现，并将其与目前对疾病机制的理解联系起来。此外，还讨论了对现有和新治疗策略的影响。
