幼年特发性关节炎与血浆特异性微小RNAs变化的关系

Relationship between specific microRNAs in plasma and juvenile idiopathic arthritis

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.