Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.
Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.
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DOI：
10.1086/590117
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发表时间：
2008-08-15
期刊：
影响因子：
--
通讯作者：
Simmons CP
中科院分区：
文献类型：
--
作者：
Chau TN;Quyen NT;Thuy TT;Tuan NM;Hoang DM;Dung NT;Lien le B;Quy NT;Hieu NT;Hieu LT;Hien TT;Hung NT;Farrar J;Simmons CP
严重登革热的发病机制尚未完全了解。母亲产生的登革病毒反应性IgG亚中和水平被认为是婴儿期严重登革的关键风险因素。在这项研究中，我们发现，在健康的越南婴儿中，纯血浆的Fc依赖性登革热病毒感染增强活性与严重登革热的年龄相关流行病学之间存在很强的时间关联。然后，我们假设原发性感染婴儿的疾病严重程度与强大的免疫应答相关，可能是体内病毒负荷较高的结果。因此，在因急性登革热住院的婴儿中，外周血NK细胞和CD 8+和CD 4 + T细胞的活化表型与总体疾病严重程度相关，但HLA-A*1101限制性NS 3133 -142特异性CD 8 + T细胞直到早期恢复才可测量。登革热休克综合征患儿血浆细胞因子/趋化因子水平普遍较高。总的来说，这些数据支持了婴儿登革热发病机制的模型，其中抗体依赖性感染增强解释了年龄相关的病例流行病学，并可以解释抗原驱动的免疫激活及其与疾病严重程度的关系。这些结果还强调了在登革热流行的国家对婴儿使用减毒活登革热疫苗的潜在风险。
The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3133-142-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.