14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis
14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis
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DOI：
10.3899/jrheum.141385
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发表时间：
2015-09-01
影响因子：
3.9
通讯作者：
Marotta, Anthony
中科院分区：
文献类型：
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作者：
Maksymowych, Walter P.;Boire, Gilles;Marotta, Anthony
Objective.目的：探讨14-3-3 eta自身抗体在早期类风湿关节炎（RA）中的表达及诊断价值。使用电致发光多重测定法测量500名受试者（114名患有早期RA的疾病缓解抗风湿药物初治患者，135名患有确定的RA，55名健康人，70名自身免疫患者和126名其他非RA关节病对照）中的14-3-3 eta自身抗体水平。14-3-3 eta蛋白水平在早期分析中测定。双尾Student t检验和Mann-Whitney U检验比较了组间差异。生成受试者-操作者特征（ROC）曲线，并通过曲线下面积（AUC）、特异性、灵敏度和最佳截止值的似然比（LR）评估诊断性能。与健康对照组（235 U/ml）、疾病对照组（274 U/ml）、自身免疫性疾病对照组（274 U/ml）、骨关节炎患者（259 U/ml）和所有对照组（265 U/ml）相比，早期RA患者（525 U/ml）的中位血清14-3-3 eta自身抗体浓度显著更高（p < 0.0001）。比较早期RA与健康对照的ROC曲线分析显示显著（p < 0.0001）AUC为0.90（95%CI 0.85-0.95）。在>= 380 U/ml的最佳截止值时，ROC曲线产生的灵敏度为73%，特异性为91%，阳性LR为8.0。在14 -3-3 eta蛋白阳性的基础上增加14 - 3 - 3 eta自身抗体，可将早期RA患者的识别率从59%提高到90%;在抗瓜氨酸蛋白抗体（ACPA）和/或类风湿因子（RF）基础上增加14-3-3 eta自身抗体，可将识别率从72%提高到92%。72%的RF和ACPA血清阴性患者14-3-3 eta自身抗体阳性。14-3-3 eta自身抗体，单独和与14-3-3 eta蛋白，RF，和/或ACPA的组合确定了大多数早期RA患者。
Objective. To describe the expression and diagnostic use of 14-3-3 eta autoantibodies in early rheumatoid arthritis (RA).Methods. 14-3-3 eta autoantibody levels were measured using an electrochemiluminescent multiplexed assay in 500 subjects (114 disease-modifying antirheumatic drug-naive patients with early RA, 135 with established RA, 55 healthy, 70 autoimmune, and 126 other non-RA arthropathy controls). 14-3-3 eta protein levels were determined in an earlier analysis. Two-tailed Student t tests and Mann-Whitney U tests compared differences among groups. Receiver-operator characteristic (ROC) curves were generated and diagnostic performance was estimated by area under the curve (AUC), as well as specificity, sensitivity, and likelihood ratios (LR) for optimal cutoffs.Results. Median serum 14-3-3 eta autoantibody concentrations were significantly higher (p < 0.0001) in patients with early RA (525 U/ml) when compared with healthy controls (235 U/ml), disease controls (274 U/ml), autoimmune disease controls (274 U/ml), patients with osteoarthritis (259 U/ml), and all controls (265 U/ml). ROC curve analysis comparing early RA with healthy controls demonstrated a significant (p < 0.0001) AUC of 0.90 (95% CI 0.85-0.95). At an optimal cutoff of >= 380 U/ml, the ROC curve yielded a sensitivity of 73%, a specificity of 91%, and a positive LR of 8.0. Adding 14-3-3 eta autoantibodies to 14-3-3 eta protein positivity enhanced the identification of patients with early RA from 59% to 90%; addition of 14-3-3 eta autoantibodies to anticitrullinated protein antibodies (ACPA) and/or rheumatoid factor (RF) increased identification from 72% to 92%. Seventy-two percent of RF-and ACPA-seronegative patients were positive for 14-3-3 eta autoantibodies.Conclusion. 14-3-3 eta autoantibodies, alone and in combination with the 14-3-3 eta protein, RF, and/or ACPA identified most patients with early RA.