Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers.
Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers.
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DOI：
10.1186/ar4431
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发表时间：
2014-01-08
影响因子：
4.9
通讯作者：
Cañete JD
中科院分区：
文献类型：
--
作者：
Ramírez J;Ruíz-Esquide V;Pomés I;Celis R;Cuervo A;Hernández MV;Pomés J;Pablos JL;Sanmartí R;Cañete JD
本研究的目的是利用功率多普勒超声（PDUS）和血清炎症和/或血管生成生物标志物水平来识别和表征临床缓解的类风湿性关节炎（RA）患者的亚临床滑膜炎。我们选择临床缓解的RA患者，定义为疾病活动评分为28关节(DAS28)-红细胞沉降率(ESR) <2.6，由两名独立的风湿病学家测试超过6个月。分析临床、流行病学、人口学和血清学资料。由超声医师对膝关节和手部进行PDUS检查。对滑膜肥厚（SH）和pdu信号进行评分（0 ~ 3级）。SH≥2且pdu信号为活动性滑膜炎。采用Quantibody®Human Array检测血清炎症/血管生成生物标志物水平。本研究纳入55例患者，其中25例（45.4%）符合超声定义的活动性滑膜炎标准。活动性滑膜炎患者DAS28-C反应蛋白（P = 0.023）、DAS28-ESR （P = 0.06）、简化疾病活动性评分、SDAI （P = 0.064）较高，且只有12%的患者口服糖皮质激素（≤5 mg/天），而非活动性滑膜炎患者的这一比例为40% （P = 0.044）。滑膜炎患者血清血管生成生物标志物血管生成素-2 （P = 0.038）、血管内皮生长因子-d （P = 0.018）、胎盘生长因子（P = 0.043）、基质细胞衍生因子-1 （P = 0.035）、基质金属肽酶-2 （P = 0.027）和碱性成纤维细胞生长因子（bFGF） （P = 0.007）水平也显著升高，但促炎细胞因子水平无显著升高。在用于探索活动性滑膜炎预后生物标志物的多变量logistic回归模型中，血清bFGF水平、DAS28-ESR和未接受糖皮质激素治疗是活动性滑膜炎的最佳预测因子。模型提供的预测指标特异性为73.3%，敏感性为72%，曲线下面积为81.5% （95% CI: 70.1% ~ 92.8%）。接近一半临床缓解的RA患者有超声诊断的活动性滑膜炎，与无活动性滑膜炎的患者相比，疾病活动性更高，口服糖皮质激素用量更少。这种临床情况与特定的生物学特征有关，其特征是血管生成介质过量，而不是持续的促炎细胞因子反应。
The aim of this study was to identify and characterize subclinical synovitis in patients with rheumatoid arthritis (RA) in clinical remission using power Doppler ultrasound (PDUS) and serum levels of biomarkers of inflammation and/or angiogenesis. We selected patients with RA in clinical remission defined as a Disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for more than six months tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer. Synovial hypertrophy (SH) and PDUS signal were scored (grades 0 to 3). SH ≥2 and a PDUS signal was classified as active synovitis. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody® Human Array. This study included 55 patients, of whom 25 (45.4%) met criteria for ultrasound-defined active synovitis. Patients with active synovitis had higher DAS28-C reactive protein (P = 0.023), DAS28-ESR (P = 0.06), simplified disease activity score, SDAI (P = 0.064), and only 12% were taking oral glucocorticoids (≤5 mg/day) compared with 40% of patients without active synovitis (P = 0.044). Patients with synovitis also had significantly higher serum levels of the angiogenic biomarkers angiopoietin-2 (P = 0.038), vascular endothelial growth factor-D (P = 0.018), placental growth factor (P = 0.043), stromal cell-derived factor-1 (P = 0.035), matrix metallopeptidase-2 (P = 0.027) and basic fibroblast growth factor (bFGF) (P = 0.007), but not of pro-inflammatory cytokines. In the multivariate logistic regression model used to explore prognostic biomarkers for active synovitis, serum levels of bFGF, DAS28-ESR and not receiving glucocorticoids were the best predictors of active synovitis. The predictive indexes provided by the model were specificity 73.3%, sensitivity 72%, and area under the curve in receiver operating characteristic 81.5% (95% CI: 70.1% to 92.8%). Nearly half of the patients with RA in clinical remission had ultrasound-defined active synovitis, higher disease activity and less frequent oral glucocorticoid consumption than patients without active synovitis. This clinical situation was associated with a specific biological profile characterized by an excess of angiogenic mediators rather than persistent proinflammatory cytokine responses.
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影响因子：
--
作者：
Saleem, Benazir;Brown, Andrew K.;Emery, Paul
通讯作者：
Emery, Paul
DOI：
10.1111/j.1749-6632.2009.05367.x
发表时间：
2010-01-01
期刊：
NEUROENDOCRINE IMMUNOLOGY IN RHEUMATIC DISEASES
影响因子：
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作者：
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通讯作者：
Caporali, Roberto
影响因子：
4.9
作者：
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通讯作者：
Jacobs JW
影响因子：
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作者：
Yoo, Seung-Ah;Yoon, Hyung-Ju;Kim, Wan-Uk
通讯作者：
Kim, Wan-Uk
影响因子：
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作者：
Izquierdo, Elena;Canete, Juan D.;Pablos, Jose L.
通讯作者：
Pablos, Jose L.