Li Fei, Liu Xiang-Ping, Li Ji-An, Han Zhen-Liang, Liu Pei-Pei, Wang Yuan-Yuan, Song Long, Chen Zong-Bo
Pediatric Department, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, People's Republic of China,
Arch Virol. 2015 Apr;160(4):1035-42. doi: 10.1007/s00705-015-2356-8. Epub 2015 Feb 10.
Enterovirus 71 (EV71) has caused many outbreaks of diseases among children worldwide since it was first reported in 1974, but its mechanism of pathogenesis remains unclear. This study was designed to investigate the possible association of the IL-4 -589C/T gene polymorphism with severity of EV71 infection in Chinese children. The IL-4 -589C/T gene polymorphism was detected in EV71-infected subjects (n = 185), including those with mild cases (n = 102) and severe cases (n = 83) as well as healthy controls (n = 234), using an improved multiplex ligation detection reaction (iMLDR) technique. The plasma levels of IL-4 and IFN-γ were determined by enzyme-linked immunosorbent assays. The presence of the CC genotype (p = 0.022) and the C allele (OR, 2.1; 95 % CI, 1.3-3.6; p = 0.004) was significantly higher in severe cases. Furthermore, the CC genotype and C allele were also more frequently found in cases of EV71 encephalitis (p < 0.05). The plasma levels of IL-4 of the CC (7.9 ± 1.3 pg/mL, p < 0.001) and CT genotype (6.8 ± 2.1 pg/mL, p < 0.01) were significantly elevated compared to those of the TT genotype, but the plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower for the CC and CT genotypes than for the TT genotype (p < 0.05). These findings suggest that the IL-4 -589C allele could be a susceptibility factor in the development of EV71 disease in Chinese children.
自1974年首次报道以来，肠道病毒71型（EV71）已在全球范围内引发了多起儿童疾病暴发，但发病机制仍不清楚。本研究旨在探讨白细胞介素-4（IL-4） -589C/T基因多态性与中国儿童EV71感染严重程度之间的可能关联。采用改进的多重连接检测反应（iMLDR）技术，对185例EV71感染患者（包括102例轻症患者和83例重症患者）以及234例健康对照者进行了IL-4 -589C/T基因多态性检测。通过酶联免疫吸附测定法测定血浆中IL-4和干扰素-γ（IFN-γ）水平。重症患者中CC基因型（p = 0.022）和C等位基因（比值比，2.1；95%可信区间，1.3 - 3.6；p = 0.004）的出现频率显著更高。此外，CC基因型和C等位基因在EV71脑炎患者中也更常见（p < 0.05）。与TT基因型相比，CC基因型（7.9 ± 1.3 pg/mL，p < 0.001）和CT基因型（6.8 ± 2.1 pg/mL，p < 0.01）患者的血浆IL-4水平显著升高，但CC和CT基因型患者的血浆IFN-γ水平及IFN-γ/IL-4比值显著低于TT基因型（p < 0.05）。这些发现表明，IL-4 -589C等位基因可能是中国儿童EV71疾病发生的一个易感因素。
