Asante R Kamkwalala1, Xuzhi Wang2, Pauline M Maki3, Dionna W Williams4,5, Victor G Valcour6, Alexandra Damron1, Phyllis C Tien7,8, Kathleen M Weber9, Mardge H Cohen9, Erin E Sundermann10, Vanessa J Meyer3, Deborah M Little11, Yanxun Xu2,12, Leah H Rubin1,13,14. 1. Departments of Neurology. 2. Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD. 3. Departments of Psychiatry and Psychology, University of Illinois at Chicago, Chicago, IL. 4. Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD. 5. Division of Clinical Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD. 6. Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA. 7. Department of Medicine, University of California, San Francisco, San Francisco, CA. 8. Department of Veterans Affairs Medical Center, San Francisco, CA. 9. CORE Center, Cook County Health and Hektoen Institute of Medicine, Chicago, IL. 10. Department of Psychiatry, University of California San Diego School of Medicine, La Jolla, CA. 11. Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX. 12. Division of Biostatistics and Bioinformatics at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD. 13. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; and. 14. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD.
Abstract
BACKGROUND: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities. METHODS: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH). RESULTS: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women. CONCLUSIONS: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.
BACKGROUND: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities. METHODS: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH). RESULTS: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women. CONCLUSIONS: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.
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