Choida Varvara, Hall-Craggs Margaret, Jebson Bethany R, Fisher Corinne, Leandro Maria, Wedderburn Lucy R, Ciurtin Coziana
Centre for Adolescent Rheumatology Versus Arthritis at UCL UCLH and GOSH, Division of Medicine, University College London, London, United Kingdom.
Department of Adolescent Rheumatology, University College London Hospital, London, United Kingdom.
Front Pharmacol. 2021 Feb 2;11:635823. doi: 10.3389/fphar.2020.635823. eCollection 2020.
Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory arthritis of childhood, characterized by various clinical phenotypes associated with variable prognosis. Significant progress has been achieved with the use of biologic treatments, which specifically block pro-inflammatory molecules involved in the disease pathogenesis. The most commonly used biologics in JIA are monoclonal antibodies and recombinant proteins targeting interleukins 1 (IL-1) and 6 (IL-6), and tumor necrosis factor α (TNF-α). Several biomarkers have been investigated in JIA. To assess the level of evidence available regarding the role of biomarkers in JIA related to guiding clinical and therapeutic decisions, providing disease prognostic information, facilitating disease activity monitoring and assessing biologic treatment response in JIA, as well as propose new strategies for biologic therapy-related biomarker use in JIA. We searched PubMed for relevant literature using predefined key words corresponding to several categories of biomarkers to assess their role in predicting and assessing biologic treatment response and clinical remission in JIA. We reviewed serological, cellular, genetic, transcriptomic and imaging biomarkers, to identify candidates that are both well-established and widely used, as well as newly investigated in JIA on biologic therapy. We evaluated their role in management of JIA as well as identified the unmet needs for new biomarker discovery and better clinical applications. Although there are no ideal biomarkers in JIA, we identified serological biomarkers with potential clinical utility. We propose strategies of combining biomarkers of response to biologics in JIA, as well as routine implementation of clinically acceptable imaging biomarkers for improved disease assessment performance.
幼年特发性关节炎（JIA）是儿童期最常见的慢性炎症性关节炎，其特征为具有不同预后的多种临床表型。生物治疗的应用取得了显著进展，生物治疗可特异性阻断参与疾病发病机制的促炎分子。JIA中最常用的生物制剂是针对白细胞介素1（IL-1）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）的单克隆抗体和重组蛋白。已有多种生物标志物在JIA中得到研究。为了评估现有证据关于生物标志物在JIA中指导临床和治疗决策、提供疾病预后信息、促进疾病活动监测及评估生物治疗反应方面的作用，并提出生物治疗相关生物标志物在JIA中应用的新策略。我们使用对应于几类生物标志物的预定义关键词在PubMed上搜索相关文献，以评估它们在预测和评估JIA生物治疗反应及临床缓解方面的作用。我们回顾了血清学、细胞、遗传、转录组学和成像生物标志物，以识别已确立且广泛使用的以及在JIA生物治疗方面新研究的候选标志物。我们评估了它们在JIA管理中的作用，并确定了新生物标志物发现和更好临床应用方面未满足的需求。尽管JIA中尚无理想的生物标志物，但我们确定了具有潜在临床应用价值的血清学生物标志物。我们提出了在JIA中联合生物制剂反应生物标志物的策略，以及常规实施临床上可接受的成像生物标志物以提高疾病评估性能的策略。
