Goutaki M, Haidopoulou K, Pappa S, Tsakiridis P, Frydas E, Eboriadou M, Hatzistylianou M
4th Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
2nd Department of Pediatrics, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Int J Immunopathol Pharmacol. 2014 Oct-Dec;27(4):563-72. doi: 10.1177/039463201402700412.
Clinical manifestations of respiratory syncytial virus (RSV) infection vary from minimal disease to severe acute bronchiolitis. The structural complex of TLR4/CD14 participates in the virus recognition as a component of natural immune response. Genetic variations of TLR4/CD14 may explain great variations in disease severity. The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis. Our study included two groups of Greek infants and young children (A and B). Group A consisted of 50 infants ≤2 years of age hospitalised with bronchiolitis and group B of 99 previously healthy children aged 4-14 years (control group) with a free past medical history. RSV was identified by PCR of genetic material that was extracted from nasopharyngeal samples collected from all patients. Blood samples were used to extract DNA and by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the development of acute bronchiolitis. For CD14 polymorphisms, a positive association was found between the C-159T and the development of bronchiolitis (p=0.05) but not for the other loci. There were no differences detected in the frequencies of the four polymorphisms studied among infants with RSV and non-RSV bronchiolitis. It is concluded that protein CD14 may have a functional role in the viral conjunction to the structural complex TLR4/CD14. The association between the polymorphism C-159T and the manifestation of disease found in our study points out that the severity in the development of acute bronchiolitis is not specified exclusively by the pathogen, but the immune response of the host also plays a significant role. More extensive multicentric studies need to take place, in order to lead to safer conclusions.
呼吸道合胞病毒（RSV）感染的临床表现从轻微疾病到严重急性细支气管炎不等。TLR4/CD14的结构复合体作为天然免疫反应的一个组成部分参与病毒识别。TLR4/CD14的基因变异可能解释疾病严重程度的巨大差异。本研究的目的是调查TLR4的Asp299Gly和Thr399Ile多态性以及CD14的C-159T和C-550T多态性在RSV细支气管炎发病中的可能作用。我们的研究包括两组希腊婴幼儿（A组和B组）。A组由50名≤2岁因细支气管炎住院的婴幼儿组成，B组由99名既往健康的4 - 14岁儿童（对照组）组成，他们既往无病史。通过对从所有患者采集的鼻咽样本中提取的遗传物质进行PCR来鉴定RSV。采集血样用于提取DNA，并使用PCR - RFLP方法进行TLR4和CD14基因分型。我们发现TLR4多态性（Asp299Gly和Thr399Ile）与急性细支气管炎的发病之间无关联。对于CD14多态性，发现C - 159T与细支气管炎的发病之间存在正相关（p = 0.05），但其他位点无此关联。在患有RSV和非RSV细支气管炎的婴幼儿中，所研究的四种多态性的频率未检测到差异。结论是，蛋白CD14可能在病毒与结构复合体TLR4/CD14的结合中发挥功能作用。我们的研究中发现的C - 159T多态性与疾病表现之间的关联指出，急性细支气管炎发病的严重程度并非仅由病原体决定，宿主的免疫反应也起着重要作用。需要进行更广泛的多中心研究，以得出更可靠的结论。
