Hull Jeremy, Rowlands Kate, Lockhart Elizabeth, Moore Catrin, Sharland Mike, Kwiatkowski Dominic
University Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford, UK.
J Infect Dis. 2003 Sep 15;188(6):904-7. doi: 10.1086/377587. Epub 2003 Sep 9.
Respiratory syncytial virus (RSV) bronchiolitis is characterized by intense inflammation of the airways, and high levels of proinflammatory cytokines and chemokines can be found in respiratory secretions of affected infants. Important among these chemokines are RANTES (regulated on activation, normal T cell-expressed and -secreted) and macrophage inflammatory-protein alpha, MIP-1alpha, both of which show correlation with severe RSV bronchiolitis. It is not clear whether high levels of these chemokines are important in disease pathogenesis, and this study addresses this question by studying genetic variants of their major receptor, CC chemokine receptor 5. Results from both a case-control and family-based genetic-association analysis show that the -2459G and -2554T variants are associated with severe RSV bronchiolitis (P=.01). It is proposed that these CCR5 variants influence the inflammatory response, and these data provide further evidence of the important role that host genetic variability plays in the determination of disease severity in RSV bronchiolitis.
呼吸道合胞病毒（RSV）细支气管炎的特征是气道强烈炎症，在受影响婴儿的呼吸道分泌物中可发现高水平的促炎细胞因子和趋化因子。这些趋化因子中重要的是调节激活正常T细胞表达和分泌因子（RANTES）和巨噬细胞炎性蛋白α（MIP-1α），二者均与严重RSV细支气管炎相关。尚不清楚这些趋化因子的高水平在疾病发病机制中是否重要，本研究通过研究其主要受体CC趋化因子受体5的基因变异来解决这一问题。病例对照研究和基于家系的基因关联分析结果均显示，-2459G和-2554T变异与严重RSV细支气管炎相关（P = 0.01）。有人提出这些CCR5变异影响炎症反应，这些数据进一步证明宿主基因变异性在RSV细支气管炎疾病严重程度的决定中起重要作用。
