摘要
目的探讨血浆特异性微小RNA(miRNA)作为幼年特发性关节炎(JIA)早期诊断标志物的可能性。方法研究分4个阶段:1.miRNA筛选:取性别和年龄匹配的JIA少关节型、JIA多关节型各5例和健康儿童3例血浆行miRNA芯片分析,选取5种候选miRNAs。2.选80例JIA(少关节型43例、多关节型37例)、幼年强直性脊柱炎(JAS)29例和健康儿童30例,采用Real—timePCR法确证这5种miRNAs能否作为生物标志物。3.观察9例JIA患者抗风湿药物治疗前后血浆miRNAs的变化。4.分析miRNAs与JIA临床参数之间的关系。结果JIA组血浆miR-16、miR-146a和miR-223的平均水平均高于健康儿童组(P均〈0.05)和JAS组(P均〈0.001),血浆miR-132和miRl55的平均水平显著低于健康儿童组和JAS组(P均〈0.001)。多关节型患儿血浆miR-16的平均水平高于少关节型患儿(P〈0.01),而miR.146a、miR-223和miR.132组间差异均无统计学意义(P均〉0.05)。抗风湿药治疗后血浆miR-16有下降趋势(P=0.061),miR-16与关节疼痛呈负相关。结论血浆miR-16可较好地区分JIA、JAS及健康儿童,但对于JIA亚型的鉴别意义有限。
Objective To investigate the potential possibilities of specific microRNA in plasma as novel bio- markers for the early diagnosis in juvenile idiopathic arthritis (JIA). Methods This research was be segmented into 4 stages. 1. Screened candidate microRNAs :5 candidate plasma microRNAs were detected by biochips of microRNAs, corresponding 5 JIA patients with onset of oligoarthritis,5 JIA patients with onset of polyarthritis and 3 age-matched and sex-matched healthy controls individual. 2. The feasibility of the microRNAs as novel biomarkers was validated by Real- time quantitative polymerase chain reaction (RT-PCR) in plasma on 80 JIA patients (43 oligoarthritis, 37 polyarthri- tis) ,29 juvenile ankylosing spondylitis(JAS) patients and 30 healthy control individuals. 3. The change of microRNAs was observed by RT-PCR in plasma from another 9 J|A patients before and 3 months after anti-rheumatic drug treat- ment. 4. The correlation between the levels of candidate plasma microRNAs and clinical parameters of JIA patients was analyzed. Results Plasma concentrations of miR-16, miR-146a and miR-223 in JIA patients, including oligoarthritis and polyarthritis, were significantly higher than those in healthy subjects ( all P 〈 O. 05 ) and JAS patients ( all P 〈 0. 001 ), and plasma concentration of miR-132 in JIA were significantly lower than those in heahhy subjects and JAS pa- tients ( all P 〈 0.001 ). Although the plasma concentration of miR-16 in polyarthritis JIA patients was considerably higher than that in oligoartbritis JIA patients (all P 〈 0.01 ),the plasma concentrations of miR-f46a, miR-223 and miR-132 were no difference between the 2 subtypes of JIA( all P 〉 0.05 ). More importantly, it was found that the ex- pression of miR-16 was considerably reduced in the post-treatment plasma samples when compared to the pre-treatment samples (P = 0. 061 ). In addition, the levels of miR-16 in JlA plasma inversely corrected with tender joint. Conclusions Plasma levels of miR-16 were well-discriminated between JIA patients and heahhy subjects or JAS patients. It is sug- gested that plasma miR-16 might serve as a novel and potential biomarker for screening JIA. Furthermore, it might serve as a novel biomarker for joint inflammation but not specifically for differentiating the subtypes of JIA.
出处
《中华实用儿科临床杂志》
CAS
CSCD
北大核心
2013年第21期1614-1618,共5页
Chinese Journal of Applied Clinical Pediatrics
基金
首都卫生发展科研专项项目(首发2011-1008-02)