Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV
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, develop...
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Frontiers Media S.A.
2020-04-01
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Series: | Frontiers in Integrative Neuroscience |
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Online Access: | https://www.frontiersin.org/article/10.3389/fnint.2020.00020/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leah H. Rubin Leah H. Rubin Leah H. Rubin Yanxun Xu Yanxun Xu Philip J. Norris Xuzhi Wang Raha Dastgheyb Kathryn C. Fitzgerald Sheila M. Keating Robert C. Kaplan Pauline M. Maki Pauline M. Maki Kathryn Anastos Kathryn Anastos Kathryn Anastos Gayle Springer Lorie Benning Seble Kassaye Deborah R. Gustafson Victor G. Valcour Dionna W. Williams Dionna W. Williams |
spellingShingle |
Leah H. Rubin Leah H. Rubin Leah H. Rubin Yanxun Xu Yanxun Xu Philip J. Norris Xuzhi Wang Raha Dastgheyb Kathryn C. Fitzgerald Sheila M. Keating Robert C. Kaplan Pauline M. Maki Pauline M. Maki Kathryn Anastos Kathryn Anastos Kathryn Anastos Gayle Springer Lorie Benning Seble Kassaye Deborah R. Gustafson Victor G. Valcour Dionna W. Williams Dionna W. Williams Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV Frontiers in Integrative Neuroscience HIV viral suppression immune cognition women |
author_facet |
Leah H. Rubin Leah H. Rubin Leah H. Rubin Yanxun Xu Yanxun Xu Philip J. Norris Xuzhi Wang Raha Dastgheyb Kathryn C. Fitzgerald Sheila M. Keating Robert C. Kaplan Pauline M. Maki Pauline M. Maki Kathryn Anastos Kathryn Anastos Kathryn Anastos Gayle Springer Lorie Benning Seble Kassaye Deborah R. Gustafson Victor G. Valcour Dionna W. Williams Dionna W. Williams |
author_sort |
Leah H. Rubin |
title |
Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV |
title_short |
Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV |
title_full |
Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV |
title_fullStr |
Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV |
title_full_unstemmed |
Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIV |
title_sort |
early inflammatory signatures predict subsequent cognition in long-term virally suppressed women with hiv |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Integrative Neuroscience |
issn |
1662-5145 |
publishDate |
2020-04-01 |
description |
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. |
topic |
HIV viral suppression immune cognition women |
url |
https://www.frontiersin.org/article/10.3389/fnint.2020.00020/full |
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doaj-c13ac68db9f84613a6b15aaeb40fa8182020-11-25T03:31:16ZengFrontiers Media S.A.Frontiers in Integrative Neuroscience1662-51452020-04-011410.3389/fnint.2020.00020511497Early Inflammatory Signatures Predict Subsequent Cognition in Long-Term Virally Suppressed Women With HIVLeah H. Rubin0Leah H. Rubin1Leah H. Rubin2Yanxun Xu3Yanxun Xu4Philip J. Norris5Xuzhi Wang6Raha Dastgheyb7Kathryn C. Fitzgerald8Sheila M. Keating9Robert C. Kaplan10Pauline M. Maki11Pauline M. Maki12Kathryn Anastos13Kathryn Anastos14Kathryn Anastos15Gayle Springer16Lorie Benning17Seble Kassaye18Deborah R. Gustafson19Victor G. Valcour20Dionna W. Williams21Dionna W. Williams22Department of Neurology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Psychiatry, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United StatesDivision of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Laboratory Medicine, Vitalant Research Institute, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Neurology, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Laboratory Medicine, Vitalant Research Institute, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Psychiatry, University of Illinois at Chicago, Chicago, IL, United StatesDepartment of Psychology, University of Illinois at Chicago, Chicago, IL, United StatesDepartment of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States0Department of General Internal Medicine, Albert Einstein College of Medicine, Bronx, NY, United States1Department of Obstetrics and Gynecology and Women’s Health, Albert Einstein College of Medicine, Bronx, NY, United StatesDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United StatesDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, United States2Department of Medicine, Georgetown University, Washington, DC, United States3Department of Neurology, SUNY Downstate Health Sciences University, Brooklyn, NY, United States4Department of Neurology, University of California, San Francisco, San Francisco, CA, United States5Department of Molecular and Comparative Pathobiology, Johns Hopkins University, Baltimore, MD, United States6Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, United StatesImmunologic 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.https://www.frontiersin.org/article/10.3389/fnint.2020.00020/fullHIVviral suppressionimmunecognitionwomen |