Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis.
Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis.
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DOI：
10.1186/s13075-016-0935-z
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发表时间：
2016-02-01
影响因子：
4.9
通讯作者：
Boire G
中科院分区：
文献类型：
--
作者：
Carrier N;Marotta A;de Brum-Fernandes AJ;Liang P;Masetto A;Ménard HA;Maksymowych WP;Boire G
年龄、C-反应蛋白（CRP）和自身抗体（Abs）与近期发病的炎性多关节炎（EPA）患者预后不良相关。血清14-3-3η蛋白是一种关节衍生的生物标志物，其上调细胞因子和酶，这些细胞因子和酶使局部和全身炎症持续存在，并可能导致关节损伤。我们的目的是在5年的前瞻性观察期内，评估EPA患者血清14-3-3η蛋白的额外预后潜力。连续收集临床变量、血清和X线片（根据Sharp/货车der Heijde（SvH）方法评分）。用斯皮尔曼相关分析法计算血清14-3-3η蛋白与其他生物标志物之间的关系。结局为简单疾病活动指数（SDAI）评分和关节损伤进展：SvH评分为ΔSvH，侵蚀组分为Δ侵蚀。采用广义估计方程（GEE）和广义线性混合模型（GLMM）确定14-3-3η的额外预测贡献。在331例患者中，分别有153例（46.2%）和119例（36.0%）患者的基线14-3-3η ≥0.19和≥0.50 ng/ml; 207例（62.5%）患者的CRP>8.0 mg/L，170例（51.5%）患者的至少一种Ab（风湿因子、抗CCP 2或抗Sa/瓜氨酸化波形蛋白）呈阳性。升高的14-3-3η水平与阳性Abs中度相关，但与升高的CRP无关。基线14-3-3η ≥0.19 ng/ml与5年内更多的放射学进展相关。通过ROC曲线确定基线14-3-3η预测放射学进展的最佳水平为0.50 ng/ml。基线时14-3-3η水平≥0.50 ng/ml与达到SDAI缓解的可能性较低（RR 0.79（95% CI 0.64-0.98），p = 0.03）以及总SvH评分和糜烂SvH评分的后续进展较高相关。随访期间14-3-3η水平升高也预示后续进展更高，即使在SDAI缓解的患者中也是如此。随访期间14-3-3η水平降低至少0.76 ng/ml并恢复为阴性，与随后较少的放射学进展相关。在多变量模型中，升高的14-3-3η与阳性Abs、升高的CRP和老年相互作用，以预测随后的放射学进展。14-3-3η蛋白水平≥0.50 ng/ml预测EPA患者在基线和治疗开始后的临床和影像学结局较差，即使在SDAI缓解者中也是如此。14-3-3η、CRP、年龄和Abs是随后关节损伤的独立预测因子。ClinicalTrials.gov ID：NCT00512239。2007年8月6日注册。本文的在线版本（doi：10.1186/s13075-016-0935-z）包含补充材料，可供授权用户使用。
Age, C-Reactive Protein (CRP) and autoantibodies (Abs) are associated with worse prognosis in patients with recent-onset inflammatory polyarthritis (EPA). Serum 14-3-3η protein is a joint-derived biomarker that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage. Our objective was to evaluate, over a 5-year prospective period of observation, the additional prognostic potential of serum 14-3-3η protein in EPA patients. Clinical variables, serum and radiographs (scored according to the Sharp/van der Heijde (SvH) method) were collected serially. Relationships between serum 14-3-3η protein and other biomarkers were computed with Spearman correlations. Outcomes were Simple Disease Activity Index (SDAI) scores and joint damage progression: ΔSvH for SvH score and ΔErosion for its Erosive component. The additional predictive contribution of 14-3-3η was defined using generalized estimating equations (GEE) and generalized linear mixed models (GLMM). Among 331 patients, baseline 14-3-3η was ≥0.19 and ≥0.50 ng/ml in 153 (46.2 %) and 119 (36.0 %), respectively; CRP was >8.0 mg/L in 207 (62.5 %), and at least one Ab (Rheumatoid Factor, anti-CCP2 or anti-Sa/citrullinated vimentin) was positive in 170 (51.5 %). Elevated 14-3-3η levels moderately correlated with positive Abs, but not with elevated CRP. Baseline 14-3-3η ≥0.19 ng/ml was associated with more radiographic progression over 5 years. The optimal levels of baseline 14-3-3η to predict radiographic progression was defined by ROC curves at 0.50 ng/ml. Levels of 14-3-3η ≥0.50 ng/ml at baseline were associated with lower likelihoods of ever reaching SDAI remission (RR 0.79 (95 % CI 0.64–0.98), p = 0.03) and higher subsequent progression of Total and Erosion SvH scores. Elevated levels of 14-3-3η during follow-up also predicted higher subsequent progression, even in patients in SDAI remission. Decreases of 14-3-3η levels by at least 0.76 ng/ml and reversion to negative during follow-up associated with less subsequent radiographic progression. In multivariate models, elevated 14-3-3η interacted with positive Abs, elevated CRP and older age to predict subsequent radiographic progression. Levels of 14-3-3η protein ≥0.50 ng/ml predict poorer clinical and radiographic outcomes in EPA, both at baseline and after initiation of treatment, even in SDAI remitters. 14-3-3η, CRP, age and Abs represent independent predictors of subsequent joint damage. ClinicalTrials.gov ID: NCT00512239. Registered August 6, 2007. The online version of this article (doi:10.1186/s13075-016-0935-z) contains supplementary material, which is available to authorized users.