Higher circulating intermediate monocytes are associated with cognitive function in women with HIV Rebecca T. Veenhuis, … , Janice E. Clements, Leah H. Rubin JCI Insight. 2021. https://doi.org/10.1172/jci.insight.146215. In-Press Preview Graphical abstract Clinical Medicine AIDS/HIV Immunology Find the latest version: https://jci.me/146215/pdf
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Higher circulating intermediate monocytes are associated withcognitive function in women with HIV
Rebecca T. Veenhuis, … , Janice E. Clements, Leah H. Rubin
Higher circulating intermediate monocytes are associated with cognitive function in women 1 with HIV 2
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Rebecca T. Veenhuis, PhD1*, Dionna W. Williams, PhD1,2*, Erin N. Shirk, MS1, Celina M. Abreu, 4 PhD1, Edna A. Ferreira, BA1, Jennifer M. Coughlin, MD3, Todd T. Brown, MD, PhD4,5, Pauline 5 M. Maki, PhD6, Kathryn Anastos, MD7, Joan W. Berman, PhD8, Janice E. Clements, PhD1,9,10, 6 and Leah H. Rubin PhD, MPH10,3,5* 7 * Equally contributing authors 8
1. Department of Molecular and Comparative Biology, Johns Hopkins University School of 9 Medicine, Baltimore, MD, USA 10
2. Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, 11 USA 12
3. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 13 Baltimore, MD, USA 14
4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA 15 5. Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, 16
Baltimore, MD, USA 17 6. Departments of Psychiatry and Psychology, University of Illinois at Chicago, Chicago, IL, USA 18 7. Departments of Medicine and Epidemiology & Population Health, Albert Einstein College of 19
Medicine, Bronx, NY, USA 20 8. Departments of Pathology and Microbiology and Immunology, Albert Einstein College of 21
Medicine, Bronx, NY, USA 22 9. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 23 10. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA 24
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Address correspondence and reprint requests to: Leah H. Rubin, Ph.D., MPH, Johns Hopkins 26 University School of Medicine, Department of Neurology, 600 N. Wolfe St, Meyer 6-113a, 27 Baltimore, MD, 21287-7613, (410)-955-7311 (phone), (410)-955-0672 (fax), email: 28 [email protected] 29 30 Running Title: Intermediate Monocytes: A Cognitive Biomarker in HIV Infected Women 31 32 Keywords: Monocytes, Cognition, HIV, women 33 34 35 36
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Monocyte subsets, cognition, HIV 2
Abbreviations 41
Human Immunodeficiency Virus (HIV); people with HIV (PWH); central nervous system (CNS); 42
women with HIV (WWH); Mononuclear cells (MNC); Toll-like receptor 2 (TLR2); 43
(Williams), U01 AI35004 (Anastos, Sharma), and pilot award funding provided to Dr. Veenhuis 543
by the JHU NIMH Center for Novel Therapeutics for HIV-associated Cognitive Disorders P30 544
MH075673. We would like to thank Dr. Joel Blankson for assessing incoming participants and 545
determining eligibility to enter our study at Johns Hopkins. We would like to thank Michelle 546
Santangelo and Abigail Matthews for their assistance with data collected at Johns Hopkins 547
University. We would like to thank all of our participants, for without you this work would not be 548
possible. 549
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Monocyte subsets, cognition, HIV 26
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Figures
Figure 1. Monocyte subset and mononuclear cell calculation for Baltimore Cohort. (A-F) A
representative FACS gating scheme. (A) Doublets were excluded using FSC-A and FSC-H
measurements, and (B) debris was gated out by drawing a gate on cell-sized events using FSC-A
and SSC-A. (C) TLR2+ cells were gated as monocytes, and non-granulocyte TLR2- cells were
gated as lymphocytes. (D) TLR2- lymphocytes were gated as CD3+ T cells or CD159a+ NK cells.
(E) CD3+ cells were then gated as CD4+ or CD8+ T cells. (F) TLR2+ monocytes were gated based
*P<0.05; ║P=0.05; †P=0.06; ‡P=0.08; TP=0.09; CES-D=Center for Epidemiologic Studies Depression Scale; PSS-10=Perceived Stress Scale; PCL-C=PTSD Checklist Civilian Version; for the mental health measures positive associations are higher monocyte subsets associating with higher symptomatology whereas negative associations are higher monocyte subsets are associated with lower symptomatology.