Department of Pathology, University of California San Diego, La Jolla, California, United States of America.
PLoS One. 2012;7(5):e32303. doi: 10.1371/journal.pone.0032303. Epub 2012 May 31.
HLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND, but also provided fewer target (activated CD4 T-cells) for HIV replication. To assess the consistency of these HLA Class II associations in a new cohort and extend analysis to HLA Class I, HLA types, neurocognitive, and virologic status were examined in a cohort of former plasma donors in China.
178 HIV infected individuals in Anhui China, were HLA typed and underwent neurocognitive evaluations (using locally standardized norms), neuromedical, treatment and virologic assessments at baseline and at 12 months.
HLA DR04 was associated with a higher rate of baseline neurocognitive impairment (p = 0.04), neurocognitive decline (p = 0.04), and lower levels of HIV RNA in plasma (p = 0.05). HLA Class I alleles (B27,57,58,A03,33) that specify a CD8 T-cell response to conserved HIV sequences were neuroprotective, associated with less impairment at baseline (p = 0.037), at month 012 (p = 0.013) and less neurocognitive decline (p = 0.023) in the interval. Consistent with the theory that effective CD8 T-cell responses require CD4 T-cell support, the HLA DR04 allele reduced the neuroprotective effect of the Class I alleles. The presence of HLA-DR*04 and the Alzheimer associated allele ApoE4 in the same individual had a synergistic negative effect on cognition (p = 0.003).
Despite major background differences between U.S. and Anhui China cohorts, HLA DR04 predicted neurocognitive impairment and lower plasma HIV RNA levels in both populations. HLA Class I alleles associated with CD8 T-cell control of HIV were associated with protection from HAND, but protection was reduced in the presence of HLA-DR04.
在美国队列中，HLA-DR*04 被确定为 HIV 相关神经认知障碍（HAND）、HIV 导致的低 CD4 T 细胞应答和低血浆 HIV RNA 水平的预测因子。我们假设低 CD4 T 细胞激活导致 HIV 在中枢神经系统中免疫控制不佳，易发生 HAND，但也为 HIV 复制提供了较少的靶标（激活的 CD4 T 细胞）。为了评估这些 HLA II 类关联在新队列中的一致性，并将分析扩展到 HLA I 类，我们在中国安徽的前血浆供者队列中检查了 HLA 类型、神经认知和病毒学状态。
中国安徽的 178 名 HIV 感染者进行了 HLA 分型，并在基线和 12 个月时进行了神经认知评估（使用当地标准化规范）、神经医学、治疗和病毒学评估。
HLA DR04 与较高的基线神经认知障碍发生率（p=0.04）、神经认知下降率（p=0.04）和较低的血浆 HIV RNA 水平（p=0.05）相关。指定对保守 HIV 序列产生 CD8 T 细胞反应的 HLA I 类等位基因（B27、57、58、A03、33）具有神经保护作用，与基线时的损伤较小相关（p=0.037）、第 012 个月时的损伤较小（p=0.013）和神经认知下降较小（p=0.023）。与有效 CD8 T 细胞反应需要 CD4 T 细胞支持的理论一致，HLA DR04 等位基因降低了 I 类等位基因的神经保护作用。同一个体中 HLA-DR*04 和阿尔茨海默病相关等位基因 ApoE4 的存在对认知有协同的负面影响（p=0.003）。
尽管美国和中国安徽队列之间存在重大背景差异，但 HLA DR04 在两个队列中均预测神经认知障碍和较低的血浆 HIV RNA 水平。与 HIV 控制相关的 HLA I 类等位基因与 HAND 的保护相关，但在 HLA-DR04 存在的情况下，保护作用降低。
