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THE alternative complement pathway in ANCA-associated vasculitis: further evidence and a meta-analysis.
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-07-21 , DOI: 10.1111/cei.13498 S Moiseev 1, 2 , J M Lee 3 , A Zykova 1, 2 , N Bulanov 1 , P Novikov 1 , E Gitel 4 , M Bulanova 5 , E Safonova 2 , J I Shin 6, 7, 8 , A Kronbichler 9 , D R W Jayne 10
Clinical & Experimental Immunology ( IF 3.4 ) Pub Date : 2020-07-21 , DOI: 10.1111/cei.13498 S Moiseev 1, 2 , J M Lee 3 , A Zykova 1, 2 , N Bulanov 1 , P Novikov 1 , E Gitel 4 , M Bulanova 5 , E Safonova 2 , J I Shin 6, 7, 8 , A Kronbichler 9 , D R W Jayne 10
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We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b‐9, and the alternative pathway components factor B and properdin in patients with ANCA‐associated vasculitis (AAV) and healthy controls, and conducted a meta‐analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta‐analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random‐effects model was used for statistical analyses. The median concentrations of MAC, C5a, C3a and factor B were higher in active AAV patients (P < 0·001). Achievement of remission was associated with reductions in C3a (P = 0·005), C5a (P = 0·035) and factor B levels (P = 0·045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered into the meta‐analysis. Plasma MAC, C5a and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Our findings and the results of the meta‐analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.
中文翻译：
ANCA 相关血管炎中的替代补体途径：进一步的证据和荟萃分析。
我们比较了 ANCA 相关血管炎 (AAV) 患者和健康对照的常见途径成分 C3a、C5a 和膜攻击复合物 (MAC)，也称为 C5b-9，以及替代途径成分因子 B 和备解素，并进行了补体激活在 AAV 发病机制中作用的现有临床证据的荟萃分析。在 59 名新诊断或复发性肉芽肿性多血管炎或显微镜下多血管炎患者和 36 名健康志愿者中评估了补体成分。在 28 名患者中，在缓解期重复检测。接下来，我们通过搜索数据库进行荟萃分析，以确定比较 AAV 患者和对照组补体水平的研究。随机效应模型用于统计分析。MAC、C5a、P < 0·001)。缓解的实现与 C3a ( P = 0·005)、C5a ( P = 0·035) 和因子 B 水平 ( P = 0·045)，而 MAC 和备解素水平没有变化。在活性 AAV 中，ANCA 特异性、疾病表型、既往免疫抑制或疾病严重程度对补体水平没有影响。共筛选出 1122 篇文章，包括本报告在内的 5 项研究进入荟萃分析。与缓解期患者（不包括因子 B）和对照组相比，活动性 AAV 患者的血浆 MAC、C5a 和因子 B 增加。C3a 的变化具有临界意义。我们的发现和荟萃分析的结果支持主要通过 AAV 患者的替代途径激活补体系统。
更新日期：2020-07-21
中文翻译：
ANCA 相关血管炎中的替代补体途径：进一步的证据和荟萃分析。
我们比较了 ANCA 相关血管炎 (AAV) 患者和健康对照的常见途径成分 C3a、C5a 和膜攻击复合物 (MAC)，也称为 C5b-9，以及替代途径成分因子 B 和备解素，并进行了补体激活在 AAV 发病机制中作用的现有临床证据的荟萃分析。在 59 名新诊断或复发性肉芽肿性多血管炎或显微镜下多血管炎患者和 36 名健康志愿者中评估了补体成分。在 28 名患者中，在缓解期重复检测。接下来，我们通过搜索数据库进行荟萃分析，以确定比较 AAV 患者和对照组补体水平的研究。随机效应模型用于统计分析。MAC、C5a、P < 0·001)。缓解的实现与 C3a ( P = 0·005)、C5a ( P = 0·035) 和因子 B 水平 ( P = 0·045)，而 MAC 和备解素水平没有变化。在活性 AAV 中，ANCA 特异性、疾病表型、既往免疫抑制或疾病严重程度对补体水平没有影响。共筛选出 1122 篇文章，包括本报告在内的 5 项研究进入荟萃分析。与缓解期患者（不包括因子 B）和对照组相比，活动性 AAV 患者的血浆 MAC、C5a 和因子 B 增加。C3a 的变化具有临界意义。我们的发现和荟萃分析的结果支持主要通过 AAV 患者的替代途径激活补体系统。
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