Imp Brandon M, Rubin Leah H, Tien Phyllis C, Plankey Michael W, Golub Elizabeth T, French Audrey L, Valcour Victor G
Memory and Aging Center, Department of Neurology.
Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey.
J Infect Dis. 2017 Jan 1;215(1):114-121. doi: 10.1093/infdis/jiw506. Epub 2016 Oct 26.
Cognitive impairment persists despite suppression of plasma human immunodeficiency virus (HIV) RNA. Monocyte-related immune activation is a likely mechanism. We examined immune activation and cognition in a cohort of HIV-infected and uninfected women from the Women's Interagency HIV Study (WIHS).
Blood levels of activation markers, soluble CD163 (sCD163), soluble CD14 (sCD14), CRP, IL-6, and a gut microbial translocation marker (intestinal fatty acid binding protein (I-FABP)) were measured in 253 women (73% HIV-infected). Markers were compared to concurrent (within ± one semiannual visit) neuropsychological testing performance.
Higher sCD163 levels were associated with worse overall performance and worse verbal learning, verbal memory, executive function, psychomotor speed, and fine motor skills (P < .05 for all comparisons). Higher sCD14 levels were associated with worse verbal learning, verbal memory, executive function, and psychomotor speed (P < .05 for all comparisons). Among women with virological suppression, sCD163 remained associated with overall performance, verbal memory, psychomotor speed, and fine motor skills, and sCD164 remained associated with executive function (P < .05 for all comparisons). CRP, IL-6, and I-FABP were not associated with worse cognitive performance.
Monocyte activation was associated with worse cognitive performance, and associations persisted despite viral suppression. Persistent inflammatory mechanisms related to monocytes correlate to clinically pertinent brain outcomes.
尽管血浆人类免疫缺陷病毒(HIV)RNA受到抑制,但认知障碍仍然存在。单核细胞相关的免疫激活可能是一种机制。我们在女性机构间HIV研究(WIHS)的一组感染HIV和未感染HIV的女性中研究了免疫激活与认知情况。
测量了253名女性(73%感染HIV)血液中激活标志物、可溶性CD163(sCD163)、可溶性CD14(sCD14)、CRP、IL-6和肠道微生物易位标志物(肠道脂肪酸结合蛋白(I-FABP))的水平。将这些标志物与同期(在±一次半年访视内)神经心理学测试表现进行比较。
较高的sCD163水平与总体表现较差、言语学习、言语记忆、执行功能、精神运动速度和精细运动技能较差相关(所有比较P<0.05)。较高的sCD14水平与言语学习、言语记忆、执行功能和精神运动速度较差相关(所有比较P<0.05)。在病毒学抑制的女性中,sCD163仍与总体表现、言语记忆、精神运动速度和精细运动技能相关,sCD164仍与执行功能相关(所有比较P<0.05)。CRP、IL-6和I-FABP与较差的认知表现无关。
单核细胞激活与较差的认知表现相关,并且尽管病毒受到抑制,这种关联仍然存在。与单核细胞相关的持续炎症机制与临床相关的脑结局相关。