Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV

Frontiers in Integrative Neuroscience

Kathryn Anastos²  Seble Kassaye³  Deborah R. Gustafson⁴  Victor G. Valcour⁵  Dionna W. Williams⁷  Xuzhi Wang⁸  Robert C. Kaplan⁹  Gayle Springer^1,10  Lorie Benning^1,10  Leah H. Rubin^1,10  Philip J. Norris^1,11  Sheila M. Keating^1,11  Kathryn C. Fitzgerald^1,12  Raha Dastgheyb^1,12  Pauline M. Maki^1,15  Yanxun Xu^1,16 

[1] 0Department of General Internal Medicine, Albert Einstein College of Medicine, Bronx, NY, United States;1Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY, United States;2Department of Medicine, Georgetown University, Washington, DC, United States;3Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States;4Department of Neurology, University of California, San Francisco, San Francisco, CA, United States;5Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, United States;6Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United States;Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United States;Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States;Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States;Department of Laboratory Medicine, Vitalant Research Institute, University of California, San Francisco, San Francisco, CA, United States;Department of Neurology, Johns Hopkins University, Baltimore, MD, United States;Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United States;Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, United States;Department of Psychology, University of Illinois at Chicago, Chicago, IL, United States;Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States;

关键词: HIV;    viral suppression;    immune;    cognition;    women;   

DOI  :  10.3389/fnint.2020.00020

来源: DOAJ

【 摘 要 】

Immunologic function is an important determinant of cognition. Here we examined the contribution of early immune signatures to cognitive performance among HIV-infected, virally suppressed women (HIV+VS) and in HIV-uninfected (HIV-) women. Specifically, we measured serum inflammatory markers, developed combinatory immune signatures, and evaluated their associations with cognition. Forty-nine HIV+VS women in the Women’s Interagency HIV Study (WIHS) who achieved viral suppression shortly after effective antiretroviral therapy (ART) initiation, and 56 matched HIV− women were selected. Forty-two serum inflammatory markers were measured within 2 years of effective ART initiation for HIV+VS women, and at an initial timepoint for HIV− women. The same inflammatory markers were also measured approximately 1, 7, and 12 years later for all women. Of the 105 women with complete immune data, 83 (34 HIV+VS, 49 HIV−) also had cognitive data available 12 years later at ≥1 time points (median = 3.1). We searched for combinatory immune signatures by adapting a dynamic matrix factorization analytic method that builds upon Tucker decomposition followed by Ingenuity® Pathway Analysis to facilitate data interpretation. Seven combinatory immune signatures emerged based on the Frobenius residual. Three signatures were common between HIV+VS and HIV− women, while four signatures were unique. These inflammatory signatures predicted subsequent cognitive performance in both groups using mixed-effects modeling, but more domain-specific associations were significant in HIV+VS than HIV− women. Leukocyte influx into brain was a major contributor to cognitive function in HIV+VS women, while T cell exhaustion, inflammatory response indicative of depressive/psychiatric disorders, microglial activity, and cytokine signaling predicted both global and domain-specific performance for HIV− women. Our findings suggest that immune signatures may be useful diagnostic, prognostic, and immunotherapeutic targets predictive of subsequent cognitive performance. Importantly, they also provide insight into common and distinct inflammatory mechanisms underlying cognition in HIV− and HIV+VS women.

【 授权许可】

Unknown