Department of Paediatrics, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
PLoS One. 2013;8(3):e58236. doi: 10.1371/journal.pone.0058236. Epub 2013 Mar 4.
Children chronically infected with hepatitis B virus (HBV) are at high risk of progressive liver disease. However, no treatment is available that is consistently effective in curing chronic hepatitis B (CHB) in children. Improved understanding of the natural course of disease is warranted. Identification of specific microRNA (miRNA) profiles in children chronically infected with HBV may provide insight into the pathogenesis of CHB and lead to advances in the management of children with CHB.
MiRNA PCR panels were employed to screen plasma levels of 739 miRNAs in pooled samples from HBeAg positive, HBeAg negative, and healthy children. The three groups' plasma miRNA profiles were compared, and aberrantly expressed miRNAs were identified. The identified miRNAs were then validated. Individual RT-qPCRs were performed on plasma from 34 HBeAg positive, 26 HBeAg negative, and 60 healthy children.
A panel of 16 plasma miRNAs were identified as aberrantly expressed in HBeAg positive and HBeAg negative children (p<0.001). Levels of all of the miRNAs were upregulated in HBeAg positive children compared with in HBeAg negative children. A positive correlation was furthermore found between plasma levels of the identified miRNAs and HBV DNA (p<0.001).
We are the first to investigate the plasma miRNA profile of children chronically infected with HBV. Our data indicates the existence of a relationship between abundance of circulating miRNAs and immunological stages in the natural course of disease. Certain miRNAs may contribute to the establishment and maintenance of CHB in children. Further studies are warranted to advance understanding of miRNAs in the pathogenesis of CHB, hopefully leading to the identification of future therapeutic targets.
慢性乙型肝炎病毒（HBV）感染的儿童存在发生进行性肝病的高风险。然而，目前尚无能够有效治愈儿童慢性乙型肝炎（CHB）的治疗方法。因此，有必要深入了解疾病的自然病程。鉴定儿童慢性 HBV 感染者特定的微小 RNA（miRNA）谱可能有助于了解 CHB 的发病机制，并推动 CHB 患儿管理的进展。
采用 miRNA PCR 试剂盒筛选 HBeAg 阳性、HBeAg 阴性和健康儿童的混合血浆样本中的 739 种 miRNA 的血浆水平。比较三组的血浆 miRNA 谱，鉴定差异表达的 miRNA。然后对鉴定出的 miRNA 进行验证。对 34 例 HBeAg 阳性、26 例 HBeAg 阴性和 60 例健康儿童的血浆进行个体 RT-qPCR。
鉴定出 16 种在 HBeAg 阳性和 HBeAg 阴性儿童中异常表达的血浆 miRNA（p<0.001）。与 HBeAg 阴性儿童相比，HBeAg 阳性儿童所有 miRNA 的水平均上调。此外，鉴定出的 miRNA 与 HBV DNA 呈正相关（p<0.001）。
我们是首次对慢性 HBV 感染儿童的血浆 miRNA 谱进行研究。我们的数据表明，循环 miRNA 的丰度与疾病自然病程中的免疫阶段之间存在相关性。某些 miRNA 可能有助于儿童 CHB 的建立和维持。进一步的研究对于深入了解 CHB 发病机制中的 miRNA 有必要，有望确定未来的治疗靶点。
