Biochemistry Department, Faculty of Pharmacy, Cairo University, 23 Kasr Al Ainy Street, Cairo, 11562, Egypt.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Mol Med. 2020 Oct 1;26(1):92. doi: 10.1186/s10020-020-00199-7.
Current blood-based tests for rheumatoid arthritis (RA) have inherent limitations, necessitating the need for additional new biomarkers for its diagnosis and monitoring disease activity and responsiveness to therapy. MicroRNAs (miRNAs) and a proliferation-inducing ligand (APRIL) are deregulated in RA and were linked to its pathogenesis. This study investigated serum levels of APRIL, miR-223 and miR-155 in RA patients, their potential as diagnostic and prognostic biomarkers, and their correlation with disease activity and clinicopathological data.
One hundred and twenty Egyptian patients with RA and 130 healthy controls were included. Serum miRNAs and APRIL were assayed by RT-qPCR and ELISA, respectively.
Serum APRIL and miR-223 were significantly upregulated, while miR-155 was unchanged in RA patients compared to controls. Serum miR-223 discriminated RA patients from controls with AUC = 0.85, whereas serum APRIL superiorly distinguished the two groups with AUC = 1 (sensitivity and specificity = 100% at cutoff> 4.19 ng/ml) by receiver-operating-characteristic analysis. Serum miR-223 was a significant predictor for RA diagnosis in multivariate logistic regression analysis. In RA group, serum APRIL was positively correlated with disease activity score (DAS28-CRP). Serum miR-223 expression was positively correlated with serum miR-155, APRIL levels and with the presence of subcutaneous nodules. Serum miR-155 levels were correlated with antinuclear antibody titer in reverse direction.
Our results suggest serum APRIL and miR-223 could serve as potential biomarkers of RA, with miR-223 as a predictor of RA risk and APRIL as an excellent biomarker of disease activity. Our data could be implicated for accurate and blood-based non-invasive diagnosis and prognosis of RA.
目前用于类风湿关节炎 (RA) 的血液检测存在固有局限性，因此需要额外的新生物标志物来诊断、监测疾病活动度和对治疗的反应。微小 RNA (miRNA) 和增殖诱导配体 (APRIL) 在 RA 中失调，与疾病发病机制有关。本研究调查了 RA 患者血清中 APRIL、miR-223 和 miR-155 的水平，及其作为诊断和预后生物标志物的潜力，以及它们与疾病活动度和临床病理数据的相关性。
纳入 120 例埃及 RA 患者和 130 例健康对照者。采用 RT-qPCR 和 ELISA 法检测血清 miRNA 和 APRIL。
与对照组相比，RA 患者血清 APRIL 和 miR-223 显著上调，而 miR-155 不变。血清 miR-223 对 RA 患者与对照组的鉴别诊断 AUC 为 0.85，而 APRIL 的 AUC 为 1（cutoff>4.19ng/ml 时灵敏度和特异度均为 100%），ROC 分析显示 APRIL 优于 miR-223。多因素 logistic 回归分析显示，血清 miR-223 是 RA 诊断的显著预测因子。在 RA 组，血清 APRIL 与疾病活动评分（DAS28-CRP）呈正相关。血清 miR-223 表达与血清 miR-155、APRIL 水平及皮下结节的存在呈正相关。血清 miR-155 水平与核抗体滴度呈负相关。
我们的研究结果表明，血清 APRIL 和 miR-223 可作为 RA 的潜在生物标志物，其中 miR-223 可预测 RA 风险，APRIL 可作为疾病活动度的优秀生物标志物。我们的数据可以为 RA 的准确、基于血液的非侵入性诊断和预后提供依据。
