Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis.
Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis.
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DOI：
10.1136/annrheumdis-2012-201981
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发表时间：
2013-08
影响因子：
27.4
通讯作者：
Merkel PA
中科院分区：
文献类型：
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作者：
Monach PA;Warner RL;Tomasson G;Specks U;Stone JH;Ding L;Fervenza FC;Fessler BJ;Hoffman GS;Iklé D;Kallenberg CG;Krischer J;Langford CA;Mueller M;Seo P;St Clair EW;Spiera R;Tchao N;Ytterberg SR;Johnson KJ;Merkel PA
以与全身性炎症标志物互补的方式鉴定区分活性抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AAV）和缓解的循环蛋白。在一项大型AAV临床试验中，在治疗前和治疗后6个月测量了代表AAV生物学不同方面的28种血清蛋白。研究了入组利妥昔单抗治疗ANCA相关血管炎（RAVE）试验的受试者（n=186）。红细胞沉降率（ESR）和C反应蛋白（CRP）水平可用于比较。主要结局是使用受试者工作特征（ROC）曲线下面积（AUC），标志物区分重度AAV（筛选时韦格纳肉芽肿伯明翰血管炎活动性评分（BVAS/WG）≥3）与缓解（第6个月时BVAS/WG=0）的能力。所有受试者在筛选时均患有重度活动性血管炎（中位BVAS/WG=8）。在第6个月缓解的137例受试者中，28种标志物中有24种显示出显著下降。ROC分析表明，CXCL 13（BCA-1）、基质金属蛋白酶-3（MMP-3）和金属蛋白酶组织抑制剂-1（TIMP-1）的水平最好地区分活动性AAV与缓解（AUC>0.8）和健康对照（AUC>0.9）。这些标志物之间的相关性以及与ESR或CRP的相关性较低。许多标志物在严重活动性AAV中升高，并随着治疗而下降，但CXCL 13，MMP-3和TIMP-1比其他研究的标志物（包括ESR和CRP）更好地区分活动性AAV与缓解。这些蛋白质是未来研究的特别有希望的候选物，以解决AAV患者评估中未满足的需求。
To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener’s granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC>0.8) and from healthy controls (AUC>0.9). Correlations among these markers and with ESR or CRP were low. Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.