Pharmacology, Toxicology and Therapeutics, University/BHF Centre for Cardiovascular Science, Edinburgh University, UK.
Institute of Biological Chemistry, Biophysics and Bioengineering, School of Engineering and Physical Science, Heriot-Watt University, UK.
Br J Clin Pharmacol. 2017 Sep;83(9):2027-2033. doi: 10.1111/bcp.13282. Epub 2017 Apr 5.
Liver-enriched microRNA-122 (miR-122) is a novel circulating biomarker for drug-induced liver injury (DILI). To date, miR-122 has been measured in serum or plasma venous samples. If miR-122 could be measured in capillary blood obtained from a finger prick it would facilitate point-of-care testing, such as in resource-limited settings that have a high burden of DILI.
In this study, in healthy subjects, miR-122 was measured by polymerase chain reaction in three capillary blood drops taken from different fingers and in venous blood and plasma (n = 20). miR-122 was also measured in capillary blood obtained from patients with DILI (n = 8).
Circulating miR-122 could be readily measured in a capillary blood drop in healthy volunteers with a median (interquartile range) cycle threshold (Ct) of 32.6 (31.1-34.2). The coefficient of variation for intraindividual variability across replicate blood drops was 49.9%. Capillary miR-122 faithfully reflected the concentration in venous blood and plasma (Pearson R = 0.89, P < 0.0001; 0.88, P < 0.0001, respectively). miR-122 was 86-fold higher in DILI patients [median value 1.0 × 10 (interquartile range 1.89 × 10 -3.04 × 10 ) copies/blood drop] compared to healthy subjects [1.85 × 10 (4.92 × 10 -5.88 × 10 ) copies/blood drop]. Receiver operator characteristic analysis demonstrated that capillary miR-122 sensitively and specifically reported DILI (area under the curve: 0.96, P = 0.0002).
This work supports the potential use of miR-122 as biomarker of human DILI when measured in a capillary blood drop. With development across DILI aetiologies, this could be used by novel point-of-care technologies to produce a minimally invasive, near-patient, diagnostic test.
富含肝组织的 microRNA-122(miR-122)是药物性肝损伤(DILI)的新型循环生物标志物。迄今为止,miR-122 已在血清或静脉血浆样本中进行了测量。如果能够在指尖采血的毛细血管血中测量 miR-122,将有助于即时检测,例如在 DILI 负担沉重的资源有限的环境中。
在这项研究中,在健康受试者中,通过聚合酶链反应测量了三个来自不同手指的毛细血管血滴以及静脉血和血浆中的 miR-122(n=20)。还测量了 DILI 患者的毛细血管血中的 miR-122(n=8)。
健康志愿者的毛细血管血滴中可以轻松测量循环 miR-122,中位数(四分位距)循环阈值(Ct)为 32.6(31.1-34.2)。个体内变异的重复血滴间变异系数为 49.9%。毛细血管 miR-122 忠实地反映了静脉血和血浆中的浓度(Pearson R=0.89,P<0.0001;0.88,P<0.0001)。与健康受试者相比,DILI 患者的 miR-122 高 86 倍[中位数为 1.0×10(四分位距为 1.89×10-3.04×10)拷贝/血滴] [1.85×10(4.92×10-5.88×10)拷贝/血滴]。受试者工作特征分析表明,毛细血管 miR-122 灵敏且特异性地报告 DILI(曲线下面积:0.96,P=0.0002)。
这项工作支持在毛细血管血滴中测量时将 miR-122 用作人类 DILI 的生物标志物。随着 DILI 病因学的发展,这可以被新的即时检测技术用于产生微创、近患者的诊断测试。