HIV infection confers distinct mechanisms in severe drug eruption: Endogenous virus activation with aberrant Th2/Th1 and CD8(+) T cells function
HIV infection confers distinct mechanisms in severe drug eruption: Endogenous virus activation with aberrant Th2/Th1 and CD8(+) T cells function
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HIV 感染导致严重药疹的机制不同：内源性病毒激活导致 Th2/Th1 和 CD8 T 细胞功能异常
DOI：
10.1111/1440-1681.13266
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发表时间：
2020
影响因子：
2.9
通讯作者：
Kuang Yi-Qun
中科院分区：
文献类型：
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作者：
Tang Jun-Ting;Li Yu-Ye;Zhang Yi;Liu Jun;Guan Wei;Wang Rui-Rui;He Li-Ping;Zhang Jian-Bo;Kuang Yi-Qun
重症药疹(SDE)是一种常见的皮肤病，当它发生在人类免疫缺陷病毒(HIV)患者身上时，就变得危险起来。然而，其分子机制却知之甚少。研究对象包括HIV+sde+(n=15)、HIV-−sde+(n=15)和HIV+sde−(n=10)。所有HIV+患者均处于获得性免疫缺陷综合征(AIDS)阶段。采用双抗体夹心法测定血清肿瘤坏死因子-α、干扰素-γ、IL-4、IL-13、IL-6、CXCL9、CCL17水平。RT-qPCR检测EB病毒(EBV)和巨细胞病毒(CMV)载量。采用流式细胞仪检测外周血中CD4、CD8、Th1、Th2、肿瘤坏死因子-α-CD8、干扰素-γ-CD8T细胞亚群。−+SDE+患者与HIVSDE+患者生化指标差异有统计学意义(P<；P<0.05)。EB病毒和巨细胞病毒载量在HIV+SDE+患者中显著升高，但在HIV−SDE+患者中无显著差异(P<；2.05)。炎性细胞因子肿瘤坏死因子-α和干扰素-γ在HIV感染者中显著升高(P<；0.05)。Th2/Th1细胞和分泌肿瘤坏死因子-α或干扰素-γ的T细胞在−+SDE+组显著高于HIV-SDE+组(P<0.05)。相反，与HIV−SDE+患者相比，HIV+SDE+患者的CD_4/CD_8比率显著下调(P<；2.05)。HIV感染在系统性红斑狼疮中具有独特的临床表型和免疫炎症机制。持续的EBV和CMV激活、Th2/Th1失衡和过度活跃的CD8+T细胞介导的促炎反应可能是HIV+SDE+患者SDE加重的不同机制。
Severe drug eruption (SDE), a common skin disease, becomes dangerous when it occurs in patients with human immunodeficiency virus (HIV). However, the molecular mechanisms are poorly understood. Forty patients including HIV+SDE+(n = 15), HIV−SDE+(n = 15) and HIV+SDE−(n = 10) subjects were enrolled in our study. All HIV+patients were at acquired immune deficiency syndrome (AIDS) stage. Serum levels of TNF‐α, IFN‐γ, IL‐4, IL‐13, IL‐6, CXCL9, and CCL17 were quantified by ELISA. Epstein–Barr virus (EBV) and cytomegalovirus (CMV) loads were quantified by RT‐qPCR. CD4, CD8, Th1, Th2, TNF‐α‐CD8, and IFN‐γ‐CD8 T cell populations were measured by flow cytometry. Levels of biochemical indexes in HIV+SDE+patients were significantly different from in HIV−SDE+patients (P< .05). EBV and CMV viral loads were significantly higher in HIV+SDE+patients, but not in HIV−SDE+patients (P< .05). Inflammatory cytokines TNF‐α and IFN‐γ were significantly elevated in HIV+SDE+patients (P< .05). Th2/Th1 populations and TNF‐α secreting or IFN‐γ secreting CD8+T cells, were significantly up‐regulated in HIV+SDE+patients compared to HIV−SDE+patients (P< .05). Conversely, the CD4/CD8 ratio was significantly down‐regulated in HIV+SDE+patients compared to HIV−SDE+patients (P< .05). HIV infection confers distinct clinical phenotypes and immune inflammatory mechanisms in SDE. Sustained EBV and CMV activation, unbalanced Th2/Th1 and overactive CD8+T cells mediating a pro‐inflammatory response could act as distinct mechanisms in the aggravation of SDE in HIV+SDE+patients.