Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
Department of Psychiatry, University of California, San Diego, CA, USA.
J Neuroimmunol. 2022 May 15;366:577845. doi: 10.1016/j.jneuroim.2022.577845. Epub 2022 Mar 12.
Monocytes and macrophages activation are crucial in human immunodeficiency virus (HIV) central nervous system (CNS) infection and HIV associated neurocognitive disorders (HAND) pathogenesis. The soluble form of CD14 (sCD14) is a marker of monocyte activation. We hypothesized that sCD14 levels would be lower in people with HIV-1 subtype C (HIV-1C) than in HIV-1B owing to a variant Tat cysteine dimotif (C30S31) with reduced chemotactic activity. A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH); 27 samples of the HIV-1B subtype and 40 of the non-B HIV-1 subtypes (including 26,HIV-1C), and 18 HIV-negative controls were included. sCD14 levels were quantified using a high-sensitivity enzyme-linked immunosorbent assay. sCD14 increase in serum, but not in CSF, was higher in samples from HIV-1B than HIV-1C (p = 0.002; Cohen's d, 0.7). CSF or serum sCD14 values were not correlated with global deficit score or specific cognitive domains. The impact of HIV-1 on monocyte stimulation biomarkers evaluated by sCD14 in serum was subtype-dependent, higher in HIV-1B than HIV-1C, consistent with reduced chemotactic activity as hypothesized.
单核细胞和巨噬细胞的激活在人类免疫缺陷病毒(HIV)中枢神经系统(CNS)感染和 HIV 相关神经认知障碍(HAND)发病机制中至关重要。可溶性 CD14(sCD14)是单核细胞激活的标志物。我们假设,由于 Tat 半胱氨酸二聚体(C30S31)的变体具有降低的趋化活性,HIV-1 型 C(HIV-1C)人群的 sCD14 水平会低于 HIV-1B。共纳入了 68 对 HIV 感染者(PWH)的脑脊液(CSF)和血液样本;其中 27 份为 HIV-1B 亚型,40 份为非 B HIV-1 亚型(包括 26 份 HIV-1C),18 份为 HIV 阴性对照。使用高灵敏度酶联免疫吸附试验定量 sCD14 水平。与 HIV-1C 相比,HIV-1B 的血清中 sCD14 增加(p = 0.002;Cohen's d,0.7),但 CSF 中没有增加。CSF 或血清 sCD14 值与总体缺陷评分或特定认知域均无相关性。血清中 sCD14 评估的 HIV-1 对单核细胞刺激生物标志物的影响取决于 HIV-1 亚型,HIV-1B 高于 HIV-1C,与假设的趋化活性降低一致。