Zhao Jiwei, Zhu Tianjun, Liao Qiu, Sun Jijia, Liu Fuqun
Department of Rheumatology and Immunology, Lishui District Traditional Hospital of Chinese Medicine, Nanjing, China.
Department of Clinical Medical, Jiangsu Health Vocational College, Nanjing, China.
BMC Rheumatol. 2025 Apr 28;9(1):49. doi: 10.1186/s41927-025-00502-1.
Effective biological markers able to monitor the response of Janus kinase inhibitor (JAKi) are lacking. Exosomal microRNAs (exomiRNAs) can alter their expression during treatment and are ideal biomarkers for therapeutic interventions. In this study, we explored potential biomarkers for monitoring tofacitinib treatment response in patients with RA.
Peripheral blood mononuclear cells (PBMCs) were collected from 35 healthy controls (HCs) and 74 patients with methotrexate (MTX)-resistant new-onset RA. We analyzed the profiles of exomiRNAs using next-generation sequencing (NGS) and verified them using quantitative real-time polymerase chain reaction (qRT-PCR). The functional roles of the selected exomiRNAs were analyzed using bioinformatics tools. Potential exomiRNAs were validated in MTX-resistant RA patients treated with tofacitinib for 3 months.
Fifty-six differentially expressed exomiRNAs were identified. High expressions of the exo-(miR-548ah-3p, miR-378 g, miR-27a-5p, and miR-30c-2-3p) were validated by qRT-PCR. Enrichment analysis indicated that these exomiRNAs may regulate immune cells and mediate immune responses. Exo-miR-27a-5p levels significantly decreased after tofacitinib treatment (p < 0.0001) and showed a strong correlation with the DAS28, RF and ESR. Receiver operating characteristic curve analysis showed that changes in the expression levels of exo-miR-27a-5p were significantly correlated with tofacitinib therapy (AUC = 0.92, p < 0.0001).
This study suggests that circulating exo-miR-27a-5p is a novel non-invasive biomarker to monitor the response to tofacitinib treatment.
目前缺乏能够监测 Janus 激酶抑制剂（JAKi）治疗反应的有效生物标志物。外泌体微小核糖核酸（外泌体 miRNAs）在治疗过程中会改变其表达，是治疗干预的理想生物标志物。在本研究中，我们探索了用于监测类风湿关节炎（RA）患者托法替布治疗反应的潜在生物标志物。
从 35 名健康对照者（HCs）和 74 名对甲氨蝶呤（MTX）耐药的新发 RA 患者中收集外周血单个核细胞（PBMCs）。我们使用下一代测序（NGS）分析外泌体 miRNAs 的谱，并使用定量实时聚合酶链反应（qRT-PCR）进行验证。使用生物信息学工具分析所选外泌体 miRNAs 的功能作用。在接受托法替布治疗 3 个月的 MTX 耐药 RA 患者中验证潜在的外泌体 miRNAs。
鉴定出 56 种差异表达的外泌体 miRNAs。通过 qRT-PCR 验证了外泌体（miR-548ah-3p、miR-378g、miR-27a-5p 和 miR-30c-2-3p）的高表达。富集分析表明，这些外泌体 miRNAs 可能调节免疫细胞并介导免疫反应。托法替布治疗后，外泌体 miR-27a-5p 水平显著降低（p < 0.0001），并且与 DAS28、RF 和 ESR 呈强相关。受试者工作特征曲线分析表明，外泌体 miR-27a-5p 表达水平的变化与托法替布治疗显著相关（AUC = 0.92，p < 0.0001）。
本研究表明，循环外泌体 miR-27a-5p 是监测托法替布治疗反应的一种新型非侵入性生物标志物。
