钙卫蛋白（S100A8/A9）与超声检测到的滑膜炎关联最为密切，并可预测生物治疗的反应：来自类风湿关节炎确诊患者纵向研究的结果
Calprotectin (S100A8/A9) has the strongest association with ultrasound-detected synovitis and predicts response to biologic treatment: results from a longitudinal study of patients with established rheumatoid arthritis.
作者信息
Nordal Hilde Haugedal, Brokstad Karl Albert, Solheim Magne, Halse Anne-Kristine, Kvien Tore K, Hammer Hilde Berner
机构信息
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Haukeland University Hospital, The Laboratory Building, 5th floor, Jonas Lies vei 87, N-5021, Bergen, Norway.
Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
出版信息
Arthritis Res Ther. 2017 Jan 12;19(1):3. doi: 10.1186/s13075-016-1201-0.
BACKGROUND
Calprotectin (S100A8/A9 or MRP8/14) and S100A12 (leukocyte-derived proteins), interleukin 6 (IL-6) and vascular endothelial growth factor (VEGF) are markers of inflammation and angiogenesis. Ultrasound (US) is sensitive for detection of greyscale synovitis and power Doppler (PD) vascularization. The objective of the present study was to explore the associations between calprotectin, S100A12, IL-6, VEGF, erythrocyte sedimentation rate, C-reactive protein and a comprehensive US assessment in patients with rheumatoid arthritis (RA) starting biologic disease-modifying anti-rheumatic drug (bDMARD) treatment.
METHODS
A total of 141 patients with RA were assessed by US, clinical examination and biomarker levels at baseline and at 1, 2, 3, 6 and 12 months after initiation of bDMARDs. US assessment of 36 joints and 4 tendon sheaths were scored semi-quantitatively (0-3 scale). European League Against Rheumatism (EULAR) response was calculated. Statistical assessments performed to explore the associations between biomarkers and US sum scores included Spearman's rank correlation analysis as well as linear and linear mixed model regression analyses.
RESULTS
Calprotectin showed the overall strongest correlations with both US sum scores (r = 0.25-0.62) and swollen joint counts (of 32) (r = 0.24-0.47) (p < 0.05 at all examinations). An association with US sum scores remained after we adjusted for age, sex, disease duration and all the other markers in a regression analysis at baseline. Decreased calprotectin at the first month was predictive of both EULAR response (p ≤ 0.001) and decreased sum PD scores at 3, 6 and 12 months (p ≤ 0.05).
CONCLUSIONS
Calprotectin had the highest association with US synovitis and predicted treatment response. It may thus be considered as a marker for evaluating inflammation and responsiveness in patients with RA on bDMARD treatment.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry (ANZCTR) identifier: ACTRN12610000284066 . Registered on 8 April 2010 (retrospectively registered).
背景
钙卫蛋白（S100A8/A9或MRP8/14）和S100A12（白细胞衍生蛋白）、白细胞介素6（IL-6）和血管内皮生长因子（VEGF）是炎症和血管生成的标志物。超声（US）对检测灰阶滑膜炎和能量多普勒（PD）血管化很敏感。本研究的目的是探讨在开始使用生物性改善病情抗风湿药（bDMARD）治疗的类风湿关节炎（RA）患者中，钙卫蛋白、S100A12、IL-6、VEGF、红细胞沉降率、C反应蛋白与全面的超声评估之间的关联。
方法
共有141例RA患者在基线以及开始使用bDMARDs后的1、2、3、6和12个月接受了超声、临床检查和生物标志物水平评估。对36个关节和4个腱鞘进行超声评估，并进行半定量评分（0 - 3分）。计算欧洲抗风湿病联盟（EULAR）反应。为探讨生物标志物与超声总分之间的关联而进行的统计评估包括Spearman等级相关分析以及线性和线性混合模型回归分析。
结果
钙卫蛋白与超声总分（r = 0.25 - 0.62）和肿胀关节数（共32个）（r = 0.24 - 0.47）的相关性总体最强（所有检查中p < 0.05）。在基线时进行的回归分析中，在对年龄、性别、病程和所有其他标志物进行校正后，其与超声总分的关联仍然存在。第一个月时钙卫蛋白降低可预测EULAR反应（p≤0.001）以及3、6和12个月时PD总分降低（p≤0.05）。
结论
钙卫蛋白与超声滑膜炎的关联最高，并可预测治疗反应。因此，它可被视为评估接受bDMARD治疗的RA患者炎症和反应性的标志物。
试验注册
澳大利亚和新西兰临床试验注册中心（ANZCTR）标识符：ACTRN12‘610’0000284066。于2010年4月8日注册（追溯注册）。
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