HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais
HLA-A and -B allele associations with secondary dengue virus infections correlate with disease severity and the infecting viral serotype in ethnic Thais
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DOI：
10.1034/j.1399-0039.2002.600405.x
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发表时间：
2002-10-01
期刊：
影响因子：
--
通讯作者：
Chandanayingyong, D
中科院分区：
文献类型：
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作者：
Stephens, HAF;Klaythong, R;Chandanayingyong, D
人们对经典 HLA-A 和 -B I 类等位基因在确定急性病毒感染的耐药性、易感性或严重性方面的作用知之甚少。急性病毒感染免疫遗传学研究的适当范例是登革热 (DF) 和登革出血热 (DHF)。登革热病毒 (DEN) 血清型 1、2、3 或 4 的原发性和继发性感染均可导致临床上较轻的 DF 或较严重的 DHF。在二次暴露中，免疫引发的个体会诱发记忆反应，这既可以清除感染性登革热病毒，又可以促进其病理学。在一项对 263 名感染 DEN-1、-2、-3 或 -4 的泰国人患者进行的病例对照研究中，我们检测到 HLA I 类与继发感染的关联，但在免疫学上未曾接受过原发感染的患者中未检测到。无论继发感染病毒血清型如何，HLA-A*0203 与较轻的 DF 相关。相比之下，HLA-A*0207 仅与继发性 DEN-1 和 DEN-2 感染的患者对更严重的 DHF 的易感性相关。相反，HLA-B*51 与继发感染患者的 DHF 发生相关，HLA-B*52 与继发 DEN-1 和 DEN-2 感染患者的 DF 相关。此外，HLA-B44、B62、B76 和 B77 似乎也能预防继发性登革热病毒感染后出现的临床疾病。这些结果证实，经典 HLA I 类等位基因与先前暴露于登革热病毒且免疫学引发的个体中暴露于登革热病毒的临床结果相关。
Little is known of the role of classical HLA-A and -B class I alleles in determining resistance, susceptibility, or the severity of acute viral infections. Appropriate paradigms for immunogenetic studies of acute viral infections are dengue fever (DF) and dengue hemorrhagic fever (DHF). Both primary and secondary infections with dengue virus (DEN) serotypes 1, 2, 3 or 4, can result in either clinically less severe DF or the more severe DHF. In secondary exposures, a memory response is induced in immunologically primed individuals, which can both clear the infecting dengue virus and contribute to its pathology. In a case-control study of 263 ethnic Thai patients infected with either DEN-1, -2, -3 or -4, we detected HLA class I associations with secondary infections, but not in immunologically naive patients with primary infections. HLA-A*0203 was associated with the less severe DF, regardless of the secondary infecting virus serotype. By contrast, HLA-A*0207 was associated with susceptibility to the more severe DHF in patients with secondary DEN-1 and DEN-2 infections only. Conversely, HLA-B*51 was associated with the development of DHF in patients with secondary infections, and HLA-B*52 was associated with DF in patients with secondary DEN-1 and DEN-2 infections. Moreover, HLA-B44, B62, B76 and B77 also appeared to be protective against developing clinical disease after secondary dengue virus infection. These results confirm that classical HLA class I alleles are associated with the clinical outcome of exposure to dengue virus, in previously exposed and immunologically primed individuals.