miR-140-3p在孤独症谱系障碍儿童中表达及其与细胞因子的相关性

Expression of miR-140-3p in children with autism spectrum disorders and its correlation with cytokines

目的探讨血清miR-140-3p在孤独症谱系障碍(ASD)儿童中表达及其与白细胞介素-4(IL-4)、白细胞介素-8(IL-8)及白细胞介素-17A(IL-17A)的相关性,为该病的诊治提供依据。方法选取2015年1月至2018年6月海南省安宁医院收治的ASD儿童172例作为病例组,另选择80例体检健康者作为对照组。采用ASD行为评定量表和儿童孤独症评定量表将172例ASD儿童分为轻-中度组(n=116)和重度组(n=56)。采用实时荧光定量聚合酶链反应(RT-PCR)和酶联免疫吸附法(ELISA)检测各组血清miR-140-3p、IL-4、IL-8及IL-17A水平变化。应用ROC曲线分析miR-140-3p、IL-4、IL-8及IL-17A对ASD的诊断价值,采用Pearson相关分析ASD儿童血清miR-140-3p与IL-4、IL-21及IL-17A的相关性。结果病例组血清miR-140-3p(0.86±0.17,0.15±0.03)、IL-4[(48.65±13.82)pg/ml,(31.42±7.50)pg/ml]、IL-8[(7.14±2.05)pg/ml,(2.30±0.74)pg/ml]及IL-17A[(112.35±51.64)pg/ml,(58.20±26.40)pg/ml]水平均明显高于对照组(P<0.05)。重度组血清miR-140-3p[(1.08±0.24),(0.71±0.12)]、IL-4[(53.28±16.30)pg/ml,(43.70±13.52)pg/ml]、IL-8[(9.42±2.85)pg/ml,(5.63±1.48)pg/ml]及IL-17A[(138.40±65.72)pg/ml,(96.74±40.83)pg/ml]水平均明显高于轻-中度组(P<0.05)。血清miR-140-3p诊断ASD的AUC(95%CI)为0.827(0.773~0.886)明显高于IL-4[0.719(0.651~0.764)pg/ml]、IL-21[0.683(0.625~0.743)pg/ml]及IL-17A[0.745(0.683~0.817)pg/ml],其最佳截值取0.75时,敏感度和特异度为84.8%和78.2%。相关分析显示,ASD儿童血清miR-140-3p与IL-4、IL-8及IL-17A均呈正相关(r=0.681、r=0.624、r=0.775,均P<0.01)。结论血清miR-140-3p水平在ASD儿童中明显升高,且与IL-4、IL-8及IL-17A水平相关,是诊断ASD的潜在生物标志物。

Objective To investigate the expression of serum miR-140-3p in children with autism spectrum disorder(ASD)and its correlation with interleukin-4(IL-4),interleukin-8(IL-8)and interleukin-17A(IL-17A),and provide evidence for the diagnosis and treatment of ASD.Methods Totally 172 cases of ASD children admitted to Anning Hospital of Hainan Province from January 2015 to June 2018 were selected as case group,80 cases of healthy subjects as control group.ASD children were divided into mild-moderate group(n=116)and severe group(n=56)by ASD Behavior Rating Scale and Child Autism Rating Scale.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to detect the changes of serum levels of miR-140-3p,IL-4,IL-8 and IL-17A in each group.ROC curve was used to analyze the diagnostic value of miR-140-3p,IL-4,IL-8 and IL-17A for ASD.Pearson correlation was used to analyze the correlation between serum miR-140-3p and IL-4,IL-8 and IL-17A in children with ASD.Results The serum levels of miR-140-3p(0.86±0.17 vs 0.15±0.03),IL-4(48.65±13.82)pg/ml vs(31.42±7.50)pg/ml),IL-8((7.14±2.05)pg/ml vs(2.30±0.74)pg/ml)and IL-17A((112.35±51.64)pg/ml vs(58.20±26.40)pg/ml)in the case group were significantly higher than those in the control group(P<0.05).Serum levels of miR-140-3p(1.08±0.24 vs 0.71±0.12),IL-4((53.28±16.30)pg/ml vs(43.70±13.52)pg/ml),IL-8((9.42±2.85)pg/ml vs(5.63±1.48)pg/ml)and IL-17A((138.40±65.72)pg/ml vs(96.74±40.83)pg/ml)in severe group were significantly higher than those in mild-moderate group(P<0.05).The AUC(95%CI)of serum miR-140-3p for ASD diagnosis was 0.827(0.773-0.886),which were significantly higher than that of IL-4(0.719(0.651-0.764)pg/ml),IL-8(0.683(0.625-0.743)pg/ml)and IL-17A(0.745(0.683-0.817)pg/ml).The best cut-off value was 0.75,and the sensitivity and specificity were 84.8%and 78.2%,respectively.The best cut-off value of serum miR-140-3p for diagnosing ASD was 0.75,and its sensitivity and specificity were 84.8%and 78.2%,respectively.The correlation analysis showed that serum miR-140-3p was positively correlated with IL-4,IL-8 and IL-17A in children with ASD(r=0.681,r=0.624,r=0.775,all P<0.01).Conclusion Serum levels of miR-140-3p was significantly higher in ASD children,correlated with levels of IL-4,IL-8 and IL-17A,and miR-140-3p was a potential biomarkers for ASD diagnosis.