识别艾滋病毒感染者使用甲基苯丙胺的预测因素:外周白细胞中的免疫多巴胺能特征和 COMT 基因型的作用

IF 3.7 Q2 IMMUNOLOGY
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引用次数: 0

摘要

由于人类病理生理学的异质性,寻找转化生物标志物的工作非常复杂,但对于疾病诊断、预后、疗效监测和患者分层至关重要。在艾滋病相关神经认知障碍(NCI)中,能描述神经发病轨迹和神经认知后遗症的生物标志物至关重要,特别是考虑到包括甲基苯丙胺(METH)在内的药物使用等混杂因素。使用甲基苯丙胺是艾滋病病毒感染者(PWH)的一个重大健康问题,尽管服用了抗逆转录病毒药物,但仍会加重认知缺陷和神经炎症,并在微环境中引入与非甲基苯丙胺使用者根本不同的因素,如高水平的多巴胺(DA)会影响 HIV-innate免疫靶点。然而,目前的生物标志物并不能检测到这些差异。我们假设,外周血白细胞中可检测到的预先定义的多巴胺诱导特征,可将 HIV+ METH 使用者与 HIV 阴性或非 METH 使用者区分开来。CD8A、CREBBP、CCL5 和多巴胺能通路转录本组合的高表达将 METH 使用者与可检测到的 CSF 病毒载量和重度抑郁障碍(MDD)聚集在一起,表明神经免疫机制之间存在联系。影响 DA 代谢的 Cathecol-o-methyltransferase (COMT) 基因多态性提高了利用生物标记物识别使用 METH 的 PWH 的能力。研究结果表明,潜在的免疫多巴胺能机制提供了特征和基因型,可以识别使用 METH 的 PWH 及其属性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identifying methamphetamine use predictors in HIV infection: Immune-dopaminergic signatures in peripheral leukocytes and the role of COMT genotype
The pursuit of translational biomarkers is complex due to the heterogeneous human pathophysiology, but critical for disease diagnosis, prognosis, monitoring therapeutic efficacy, and for patient stratification. In HIV-associated neurocognitive impairment (NCI), biomarkers that delineate the trajectory of neuropathogenesis and neurocognitive sequelae are critical, particularly considering confounders such as substance use, including Methamphetamine (METH). METH use is a significant health concern among persons living with HIV (PWH), aggravating cognitive deficits and neuroinflammation despite of antiretrovirals, introducing elements in the microenvironment that are fundamentally differerent in relation to non-METH users, such as high levels of dopamine (DA) affecting HIV-innate immune targets. Yet, current biomarkers do not detect these differences. We hypothesized that predefined DA-induced signatures detectable in peripheral blood leukocytes, can distinguish HIV+ METH users compared to HIV-negative or PWH that are non METH users. The elevated expression of CD8A, CREBBP, CCL5, and combinations of dopaminergic pathway transcripts clustered METH users with detectable CSF viral load and major depressive disorder (MDD), indicating neuroimmune-mechanistic links. Cathecol-o-methyltransferase (COMT) gene polymorphisms affecting DA metabolism improved the identification of PWH using METH with biomarkers. The results indicate that underlying immunedopaminergic mechanisms provide signatures and genotypes that can identify PWH that are METH users and their attributes.
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来源期刊
Brain, behavior, & immunity - health
Brain, behavior, & immunity - health Biological Psychiatry, Behavioral Neuroscience
CiteScore
8.50
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审稿时长
97 days
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