Abstract

The lack of specific clinical symptoms for patients in the early stage of rheumatoid arthritis (RA) has created strong interest in the laboratory diagnosis of RA. The main laboratory markers of RA, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), can be found in patients with other pathologies and in healthy donors. Even today, there is no single laboratory test that can diagnosis RA with high sensitivity and specificity. To improve the diagnosis and treatment of RA, alternative biomarkers, including 14-3-3η protein, connective tissue growth factor (CTGF), antibodies against PAD4, antibodies against BRAF, and anti-acetylated and anti-carbamylated protein antibodies have been studied extensively. The use of a multiple biomarker approach, the simultaneous measurement of a set of biomarkers, is an alternative strategy for the diagnosis of RA and for predicting the therapeutic effect of biological disease-modifying antirheumatic drugs (DMARDs). However, despite the large number of studies, only a few biomarker combinations have been validated and can be applied in clinical practice. In this article, results of studies focused on the multiple biomarker approach (both multiplex and combined single-analyte assays) to diagnose RA and to predict response to biological drug therapy are reviewed. Additionally, general factors limiting the use of multiplex analysis in RA diagnostics and therapy are discussed.

摘要

类风湿关节炎 (RA) 早期患者缺乏特异​​性临床症状，这引起了人们对 RA 实验室诊断的浓厚兴趣。RA、类风湿因子 (RF) 和抗瓜氨酸蛋白抗体 (ACPA) 的主要实验室标志物可以在患有其他疾病的患者和健康供体中找到。即使在今天，也没有单一的实验室测试可以以高灵敏度和特异性诊断 RA。为了改善 RA 的诊断和治疗，替代生物标志物，包括 14-3-3η 蛋白、结缔组织生长因子 (CTGF)、针对 PAD4 的抗体、针对 BRAF 的抗体以及抗乙酰化和抗氨甲酰化蛋白抗体已被广泛研究. 使用多种生物标志物方法，同时测量一组生物标志物，是诊断 RA 和预测生物疾病改善抗风湿药物 (DMARDs) 治疗效果的替代策略。然而，尽管进行了大量研究，但只有少数生物标志物组合得到了验证并可以应用于临床实践。在本文中，综述了侧重于多种生物标志物方法（多重和组合的单一分析物测定）诊断 RA 和预测对生物药物治疗的反应的研究结果。此外，还讨论了限制在 RA 诊断和治疗中使用多重分析的一般因素。只有少数生物标志物组合已得到验证并可应用于临床实践。在本文中，综述了侧重于多种生物标志物方法（多重和组合的单一分析物测定）诊断 RA 和预测对生物药物治疗的反应的研究结果。此外，还讨论了限制在 RA 诊断和治疗中使用多重分析的一般因素。只有少数生物标志物组合已得到验证并可应用于临床实践。在本文中，综述了侧重于多种生物标志物方法（多重和组合的单一分析物测定）诊断 RA 和预测对生物药物治疗的反应的研究结果。此外，还讨论了限制在 RA 诊断和治疗中使用多重分析的一般因素。