Anderson Albert M, Lennox Jeffrey L, Mulligan Mark M, Loring David W, Zetterberg Henrik, Blennow Kaj, Kessing Cari, Koneru Rajeth, Easley Kirk, Tyor William R
Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 341 Ponce de Leon Avenue, Atlanta, GA, 30308, USA.
Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA.
J Neurovirol. 2017 Feb;23(1):106-112. doi: 10.1007/s13365-016-0466-z. Epub 2016 Jul 11.
HIV-associated neurocognitive disorders (HANDs) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNα) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV-associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNα and neurocognitive performance in ambulatory HIV-infected individuals with milder impairment. An eight-test neuropsychological battery representing six cognitive domains was administered. Individual scores were adjusted for demographic characteristics, and a composite neuropsychological score (NPT-8) was calculated. IFNα and CSF neurofilament light chain (NFL) levels were measured using enzyme-linked immunosorbent assay (ELISA). There were 15 chronically infected participants with a history of significant immunocompromise (median nadir CD4+ of 49 cells/μl). Most participants were neurocognitively impaired (mean global deficit score of 0.86). CSF IFNα negatively correlated with three individual tests (Trailmaking A, Trailmaking B, and Stroop Color-Word) as well as the composite NPT-8 score (r = -0.67, p = 0.006). These negative correlations persisted in multivariable analyses adjusting for chronic hepatitis B and C. Additionally, CSF IFNα correlated strongly with CSF NFL, a marker of neuronal damage (rho = 0.748, p = 0.0013). These results extend findings from individuals with severe HIV-associated dementia in the pre-cART era and suggest that IFNα may continue to play a role in HAND pathogenesis during the cART era. Further investigation into the role of IFNα is indicated.
与人类免疫缺陷病毒（HIV）相关的神经认知障碍（HANDs）仍然很常见，并且与发病率和死亡率的增加有关。然而，在联合抗逆转录病毒疗法（cART）时代，其潜在机制尚未完全明确。在cART时代之前，α干扰素（IFNα）是一种抗病毒细胞因子，在患有晚期HIV相关痴呆症患者的脑脊液（CSF）中水平升高。在这项横断面研究中，我们调查了轻度受损的非卧床HIV感染个体中IFNα与神经认知表现之间的关联。我们实施了一个代表六个认知领域的八项测试的神经心理成套测验。根据人口统计学特征对个体得分进行了调整，并计算了综合神经心理得分（NPT-8）。使用酶联免疫吸附测定（ELISA）测量IFNα和脑脊液神经丝轻链（NFL）水平。共有15名有严重免疫功能低下病史的慢性感染参与者（CD4 +细胞最低点中位数为49个/μl）。大多数参与者存在神经认知障碍（平均整体缺陷评分为0.86）。脑脊液IFNα与三项个体测试（连线测验A、连线测验B和Stroop颜色-文字测验）以及综合NPT-8得分呈负相关（r = -0.67，p = 0.006）。在对慢性乙型和丙型肝炎进行校正的多变量分析中，这些负相关关系依然存在。此外，脑脊液IFNα与神经元损伤标志物脑脊液NFL密切相关（rho = 0.748，p = 0.0013）。这些结果扩展了cART时代之前患有严重HIV相关痴呆症个体的研究发现，并表明在cART时代，IFNα可能继续在HAND发病机制中发挥作用。有必要对IFNα的作用进行进一步研究。
