连续检测PR3-ANCA水平可有效预测血管炎的复发

作者：Fussner LA, et al.

翻译：北医三院李常虹摘要 目的：抗中性粒细胞胞浆抗体（ANCA）相关性血管炎出现诱导缓解后复发很常见，尤其是蛋白酶3（PR3）阳性的患者。本研究旨在评估PR3-ANCA水平升高与随后疾病复发之间的关系。

方法：本研究的资料来自于利妥昔单抗vs环磷酰胺治疗ANCA相关性血管炎的临床研究试验。自达到完全缓解起，采用直接和捕获酶联免疫吸附试验（ELISA）系列检测93例患者患者血清中的PR3-ANCA水平。

结果：93例患者中有58例患者经直接ELISA法检测发现了PR3-ANCA的升高，有59例患者捕获ELISA法检测发现了PR3-ANCA的升高。93例患者中有55例出现了疾病的复发，经直接或捕获ELISA法检测后1年内分别有25例和21例患者出现了复发。直接ELISA法检测PR3-ANCA升高与随后疾病严重复发相关，尤其是有肾脏受累和肺泡出血的患者。两种检测方法均在利妥昔单抗治疗组发现了严重复发增加的风险，而在环磷酰胺/硫唑嘌呤治疗组未发现类似的提示。

结论：PR3-ANCA水平的升高与随后疾病复发风险之间的关系部分受PR3-ANCA检测方法、疾病表型、缓解诱导治疗方案的影响。完全缓解后PR3-ANCA水平升高提示有疾病复发的风险，尤其是肾脏受累、肺泡出血和接受利妥昔单抗治疗患者的严重复发。系列检测PR3-ANCA水平在部分患者中对于预测复发有重要提示作用，但复发风险应仔细权衡治疗相关的风险。

附全文：Abstract OBJECTIVE: Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse.METHODS: Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme-linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3-ANCA, using Cox proportional hazards regression.RESULTS: An increase in PR3-ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (hr 7.94; p < 0.001) and alveolar hemorrhage (hr 24.19; p < 0.001). both assays identified increased risk for severe relapse in the rituximab group (hr 5.80; p?="?0.002" for direct elisa and hr 4.54; p?="?0.007" for capture elisa) but not the cyclophosphamide/azathioprine group (p?="?0.103" and p?="?0.197," respectively). conclusion: the association of an increase in pr3-anca level with the risk of subsequent relapse is partially affected by the pr3-anca detection methodology, disease phenotype, and remission induction treatment. an increase in pr3-anca level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. serial measurements of pr3-anca may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.

引自：Fussner LA, Hummel AM, Schroeder DR, Silva F, Cartin-Ceba R, Snyder MR, Hoffman GS, Kallenberg CG, Langford CA, Merkel PA, Monach PA, Seo P, Spiera RF, William St Clair E, Tchao NK, Stone JH, Specks U; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group.Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3. Arthritis Rheumatol. 2016 Jul;68(7):1700-10. doi: 10.1002/art.39637.