IL28B, IL29 and micro-RNA 548 in subacute sclerosing panencephalitis as a rare disease
IL28B, IL29 and micro-RNA 548 in subacute sclerosing panencephalitis as a rare disease
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DOI：
10.1016/j.gene.2018.07.062
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发表时间：
2018-12-15
期刊：
影响因子：
3.5
通讯作者：
Piskin, Ibrahim Etem
中科院分区：
文献类型：
--
作者：
Genc, Gunes Cakmak;Dursun, Ahmet;Piskin, Ibrahim Etem
亚急性硬化性全脑炎（SSPE）是一种进行性神经退行性疾病，影响儿童和年轻人，由缺陷型麻疹病毒的持续感染引起。IFN-λ（IL-28 A、IL-28 B和IL-29）是一组介导抗病毒应答的细胞因子。已经表明，在具有缺陷麻疹病毒的感染细胞中，IL-29水平显著更高。IL-29的表达被认为是在转录后水平调节的，并且miRNA-548家族靶向IFNL 1基因的3 'UTR。免疫系统受损和病毒因素在SSPE中起重要作用。本研究的目的是调查IL-28 B、IL-29水平和基因多态性是否有助于导致SSPE发展的受损免疫应答。检测64例SSPE患者和68例健康对照者的rs 12979860、rs 8099917、rs30461基因频率、血清IL-28 B、IL-29水平以及miR-548 b、miR-548 c、miR-548 i的表达水平。SSPE患者的血清IL-29水平在统计学上显著更高。rs 8099917的等位基因频率在SSPE患者中统计学上显著更高，并且发现所产生的G等位基因使SSPE的风险增加2.183倍。miR-548 b-5 p、miR-548 c-5 p和miR-548 i在SSPE患者中的表达水平显著升高，IL-29水平显著升高，表明miR-548表达升高是免疫系统反应过度激活的代偿结果。对IL 28、IL 29及其相关miRNA的进一步研究将有助于阐明SSPE的发病机制。
Subacute sclerosing panencephalitis (SSPE) is a progressive neurodegenerative disease which affects children and young adults, caused by a persistent infection of defective measles virus. IFN-lambda s (IL-28A, IL-28B and IL-29) are a group of cytokines mediating antiviral responses. It has been shown that IL-29 levels are significantly higher in infected cells with defective measles virus. IL-29 expression is thought to be regulated at post-transcriptional level and miRNA-548 family targets the 3'UTR of the IFNL1 gene. Impaired immune system has an important role as well as viral factors in SSPE. The aim of our study investigates whether IL-28B, IL-29 levels and gene polymorphisms contribute to the damaged immune response leading to the development of SSPE. Also possible association of miR-548 family with IL-29 and SSPE is explored.Frequencies of rs12979860, rs8099917, rs30461, serum levels of IL-28B, IL-29 and expression levels of miR-548b, miR-548c, miR-548i are determined at 64 SSPE patients and 68 healthy controls. Serum IL-29 levels are statistically significant higher in SSPE patients. Allele frequencies of rs8099917 are statistically significant higher in SSPE patients and resulted G allele is found to increase 2.183-fold risk of SSPE. The expression levels of miR-548b-5p, miR-548c-5p and miR-548i are found to be statistically significant higher in SSPE patients.Dramatically increased level of IL-29 seen in patient group indicates that the elevated miR-548 expression is compensatory result of the over-activated immune system response. Further studies referred to IL28, IL29 and related miRNA's will be enlightened the pathogenesis of SSPE.