抗细胞因子治疗与类风湿关节炎患者的血浆 DNA。
Anti-cytokine therapy and plasma DNA in patients with rheumatoid arthritis.
机构信息
Institute of Molecular Biomedicine, Faculty of Medicine, Comenius University, Sasinkova 4, 811 08, Bratislava, Slovakia.
National Institute of Rheumatic Diseases, Piešťany, Slovakia.
出版信息
Rheumatol Int. 2018 Aug;38(8):1449-1454. doi: 10.1007/s00296-018-4055-8. Epub 2018 May 23.
BACKGROUND
Extracellular DNA (ecDNA) is increased in inflammation and it also induces inflammation. In patients with rheumatoid arthritis (RA), plasma ecDNA is higher than in healthy controls. Due to low specificity, it cannot be used for screening, but it might be useful for monitoring and prognosis of therapy success. The effect of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) on plasma ecDNA in RA patients with regards to its subcellular origin has not been analyzed yet. The aim of this study was to describe the effects of bDMARDs on plasma ecDNA and its nuclear (nDNA) and mitochondrial (mtDNA) fractions in patients with RA.
METHODS
Plasma samples of 32 patients with RA were collected before, as well as 3 and 6 months after starting the treatment with bDMARDs. Total plasma ecDNA was quantified fluorometrically. The subcellular origin of ecDNA was assessed using real time PCR. Treatment success was monitored using DAS28 and C-reactive protein (CRP).
RESULTS
The clinical status of patients improved. Both DAS28 and CRP decreased by 52 and 73% after 3 months of treatment. Plasma ecDNA decreased significantly only after 6 months (by 26%). Real-time PCR showed that both, nDNA and mtDNA decreased by 63 and by 45% after 6 months.
CONCLUSION
Treatment with bDMARDs decreases plasma ecDNA of both nuclear and mitochondrial origin. Dynamics of ecDNA is slower than dynamics of standard clinical markers. Therefore, it is likely to be not useful for monitoring of the disease progress, at least for RA.
背景
细胞外 DNA（ecDNA）在炎症中增加，它也会引发炎症。在类风湿关节炎（RA）患者中，血浆 ecDNA 高于健康对照组。由于特异性低，不能用于筛查，但可能对监测和治疗效果的预后有用。然而，尚未分析生物疾病修饰抗风湿药物（bDMARDs）治疗对 RA 患者血浆 ecDNA 的影响及其亚细胞起源。本研究旨在描述 bDMARDs 对 RA 患者血浆 ecDNA 及其核（nDNA）和线粒体（mtDNA）部分的影响。
方法
收集 32 例 RA 患者治疗前、治疗后 3 个月和 6 个月的血浆样本。采用荧光定量法检测总血浆 ecDNA。采用实时 PCR 评估 ecDNA 的亚细胞起源。采用 DAS28 和 C 反应蛋白（CRP）监测治疗效果。
结果
患者的临床状况得到改善。治疗 3 个月后，DAS28 和 CRP 分别降低 52%和 73%。血浆 ecDNA 仅在治疗 6 个月后显著降低（降低 26%）。实时 PCR 显示，治疗 6 个月后，nDNA 和 mtDNA 分别降低 63%和 45%。
结论
bDMARDs 治疗可降低核和线粒体来源的血浆 ecDNA。ecDNA 的动态变化比标准临床标志物的动态变化慢。因此，它可能不适用于监测疾病进展，至少对 RA 不适用。
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