Carolyn Ross, Jean-Paul Makhzoum, Christian Pagnoux
{"title":"anca相关血管炎的最新进展。","authors":"Carolyn Ross, Jean-Paul Makhzoum, Christian Pagnoux","doi":"10.5152/eujrheum.2022.20248","DOIUrl":null,"url":null,"abstract":"<p><p>Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg - Strauss syndrome). Renal-limited AAV can be considered a fourth entity. Despite their rarity and still unknown cause(s), research into AAV has been very active over the past decades and has allowed for the development of new therapeutic regimens. The pathogenesis is a complex process of immune dysregulations with genetic and environmental influences. Recent genome-wide association studies have identified multiple genetic predisposing variants, especially at the major histocompatibility complex region. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) is well supported by several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) is not as strongly demonstrated. B cells likely play a major role in the pathogenesis because they produce ANCAs, as do neutrophil abnormalities, imbalances in T-cell subtypes, and/or cytokine - chemokine networks. The role of the alternative complement pathway was established more recently, and studies of the antagonist of human C5a receptor (avacopan) in AAV have just been completed, with promising results. The current standard management of severe AAV still consists of remission induction therapy with glucocorticoids combined with rituximab or, less often now, cyclophosphamide. Several studies showed that reduced-dose regimens of glucocorticoids are noninferior to the previously used heavier regimens, for therefore less cumulative exposure to glucocorticoids. Avacopan use may even lead to new steroid-free therapeutic approaches, at least for some selected patients. Several trials and studies have now shown the superiority of rituximab over azathioprine or methotrexate as maintenance therapy. However, the optimal dosing regimen and duration for maintenance remain to be better defined, at the individual patient level. Many changes have occurred in the standard of care for AAV over the past decades, and more are expected soon, including with use of avacopan, but also, likely, a few other agents under investigation or development.</p>","PeriodicalId":12066,"journal":{"name":"European journal of rheumatology","volume":"9 3","pages":"153-166"},"PeriodicalIF":1.3000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":"{\"title\":\"Updates in ANCA-associated vasculitis.\",\"authors\":\"Carolyn Ross, Jean-Paul Makhzoum, Christian Pagnoux\",\"doi\":\"10.5152/eujrheum.2022.20248\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg - Strauss syndrome). Renal-limited AAV can be considered a fourth entity. Despite their rarity and still unknown cause(s), research into AAV has been very active over the past decades and has allowed for the development of new therapeutic regimens. The pathogenesis is a complex process of immune dysregulations with genetic and environmental influences. Recent genome-wide association studies have identified multiple genetic predisposing variants, especially at the major histocompatibility complex region. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) is well supported by several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) is not as strongly demonstrated. B cells likely play a major role in the pathogenesis because they produce ANCAs, as do neutrophil abnormalities, imbalances in T-cell subtypes, and/or cytokine - chemokine networks. The role of the alternative complement pathway was established more recently, and studies of the antagonist of human C5a receptor (avacopan) in AAV have just been completed, with promising results. The current standard management of severe AAV still consists of remission induction therapy with glucocorticoids combined with rituximab or, less often now, cyclophosphamide. Several studies showed that reduced-dose regimens of glucocorticoids are noninferior to the previously used heavier regimens, for therefore less cumulative exposure to glucocorticoids. Avacopan use may even lead to new steroid-free therapeutic approaches, at least for some selected patients. Several trials and studies have now shown the superiority of rituximab over azathioprine or methotrexate as maintenance therapy. However, the optimal dosing regimen and duration for maintenance remain to be better defined, at the individual patient level. 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引用次数: 5
摘要
抗中性粒细胞细胞质抗体(ANCA)相关血管炎(AAV)是小血管血管炎,包括肉芽肿病合并多血管炎(原Wegener肉芽肿病)、显微镜下的多血管炎和嗜酸性肉芽肿病合并多血管炎(Churg - Strauss综合征)。肾受限型AAV可被视为第四个实体。尽管AAV罕见且病因不明,但在过去的几十年里,对AAV的研究一直非常活跃,并为新的治疗方案的开发提供了条件。其发病机制是一个复杂的免疫失调过程,受遗传和环境的影响。最近的全基因组关联研究已经确定了多种遗传易感变异,特别是在主要组织相容性复合体区域。抗髓过氧化物酶ANCA (MPO-ANCA)的致病作用已得到多种动物模型的支持,但抗蛋白酶3 ANCA (PR3-ANCA)的致病作用尚未得到充分证实。B细胞可能在发病机制中起主要作用,因为它们产生anca,中性粒细胞异常、t细胞亚型失衡和/或细胞因子-趋化因子网络也会产生anca。替代补体途径的作用是最近才确立的,而人类C5a受体拮抗剂(avacopan)在AAV中的研究刚刚完成,结果很有希望。目前严重AAV的标准治疗仍然包括糖皮质激素联合利妥昔单抗或环磷酰胺(现在较少使用)的缓解诱导治疗。几项研究表明,减少糖皮质激素剂量的方案并不逊于以前使用的更大剂量方案,因此减少了糖皮质激素的累积暴露。Avacopan的使用甚至可能导致新的无类固醇治疗方法,至少对于一些选定的患者。一些试验和研究表明,作为维持治疗,利妥昔单抗优于硫唑嘌呤或甲氨蝶呤。然而,在个体患者水平上,最佳给药方案和维持时间仍有待更好地确定。在过去的几十年里,AAV的治疗标准发生了许多变化,预计很快会有更多的变化,包括使用avacopan,但也可能有其他一些正在研究或开发的药物。
Antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) are small-vessel vasculitides that include granulomatosis with polyangiitis (formerly Wegener's granulomatosis), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (Churg - Strauss syndrome). Renal-limited AAV can be considered a fourth entity. Despite their rarity and still unknown cause(s), research into AAV has been very active over the past decades and has allowed for the development of new therapeutic regimens. The pathogenesis is a complex process of immune dysregulations with genetic and environmental influences. Recent genome-wide association studies have identified multiple genetic predisposing variants, especially at the major histocompatibility complex region. The pathogenic role of antimyeloperoxidase ANCA (MPO-ANCA) is well supported by several animal models, but that of antiproteinase 3 ANCA (PR3-ANCA) is not as strongly demonstrated. B cells likely play a major role in the pathogenesis because they produce ANCAs, as do neutrophil abnormalities, imbalances in T-cell subtypes, and/or cytokine - chemokine networks. The role of the alternative complement pathway was established more recently, and studies of the antagonist of human C5a receptor (avacopan) in AAV have just been completed, with promising results. The current standard management of severe AAV still consists of remission induction therapy with glucocorticoids combined with rituximab or, less often now, cyclophosphamide. Several studies showed that reduced-dose regimens of glucocorticoids are noninferior to the previously used heavier regimens, for therefore less cumulative exposure to glucocorticoids. Avacopan use may even lead to new steroid-free therapeutic approaches, at least for some selected patients. Several trials and studies have now shown the superiority of rituximab over azathioprine or methotrexate as maintenance therapy. However, the optimal dosing regimen and duration for maintenance remain to be better defined, at the individual patient level. Many changes have occurred in the standard of care for AAV over the past decades, and more are expected soon, including with use of avacopan, but also, likely, a few other agents under investigation or development.