Humanitas Clinical and Research Center - IRCCS, 20089, Rozzano, Milan, Italy.
Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, Netherlands.
Autoimmun Rev. 2021 Mar;20(3):102759. doi: 10.1016/j.autrev.2021.102759. Epub 2021 Jan 18.
Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies, predominantly IgG, involved in the pathogenesis of several autoimmune disorders, detected either through indirect immunofluorescence or enzyme-linked immunosorbent assay. By means of indirect immunofluorescence, the main patterns are C-ANCA (cytoplasmic) and P-ANCA (perinuclear), while proteinase 3 (PR3) and myeloperoxidase (MPO) represent the main autoantigens in granulomatosis with polyangiitis and microscopic polyangiitis, both belonging to the family of ANCA-associated vasculitis (AAV). While several experiments established the pathogenicity of MPO-ANCA, evidence remains elusive for PR3-ANCA and an additional target antigen, i.e. LAMP2, has been postulated with specific clinical relevance. The presence of a subset of AAV without ANCA may be explained by the presence of further target antigens or the presence of molecules in blood which make ANCA undetectable. A rise in ANCA titers is not necessarily predictive of a flare of disease in AAV if not accompanied by clinical manifestations. ANCA may develop through variable mechanisms, such as autoantigen complementarity, apoptosis impairment, neutrophil extracellular traps dysfunction and molecular mimicry. We will provide herein a comprehensive review of the available evidence on the biological mechanisms, pathogenetic role, and clinical implications of ANCA testing and disease management. Further, we will address the remaining open challenges in the field, including the role of ANCA in inflammatory bowel disease and in cocaine-induced vasculitis.
抗中性粒细胞胞浆抗体 (ANCA) 是一组自身抗体，主要为 IgG，参与多种自身免疫性疾病的发病机制，通过间接免疫荧光或酶联免疫吸附试验检测。通过间接免疫荧光，主要模式为 C-ANCA（细胞质）和 P-ANCA（核周），而蛋白酶 3 (PR3) 和髓过氧化物酶 (MPO) 代表肉芽肿性多血管炎和显微镜下多血管炎的主要自身抗原，两者均属于抗中性粒细胞胞浆抗体相关性血管炎 (AAV) 家族。虽然多项实验确立了 MPO-ANCA 的致病性，但 PR3-ANCA 和一个额外的靶抗原（即 LAMP2）的证据仍不清楚，并且具有特定的临床相关性。一些 AAV 患者没有 ANCA 的存在可以通过存在其他靶抗原或血液中存在使 ANCA 无法检测到的分子来解释。如果没有伴随临床表现，ANCA 滴度的升高并不一定预示着 AAV 疾病的复发。ANCA 可能通过可变机制发展，例如自身抗原互补、细胞凋亡障碍、中性粒细胞细胞外陷阱功能障碍和分子模拟。我们将在此提供关于 ANCA 检测和疾病管理的生物学机制、发病作用和临床意义的现有证据的综合回顾。此外，我们将解决该领域中剩余的未解决的挑战，包括 ANCA 在炎症性肠病和可卡因诱导的血管炎中的作用。
