Journal
AIDS
Volume 32, Issue 7, Pages 945-954Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001771
Keywords
AIDS-associated non-Hodgkin lymphoma; HIV; macrophage activation; microbial translocation
Categories
Funding
- National Institute of Health (NIH) [P30-AI-028697, R01-CA-168482, R01-CA-168482-S]
- UCLA AIDS Institute
- UCLA Center for AIDS Research [AI28697]
- UCLA Jonsson Comprehensive Cancer Center [CA016042]
- Pendleton Charitable Trust
- McCarthy Family Foundation
- Johns Hopkins University Bloomberg School of Public Health [U01-AI35042]
- Northwestern University [U01-AI35039]
- University of California, Los Angeles [U01-AI35040]
- University of Pittsburgh (Charles Rinaldo) [U01-AI35041]
- Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D'Souza) [UM1-AI35043]
- National Institute of Allergy and Infectious Diseases (NIAID)
- National Cancer Institute (NCI)
- National Institute on Drug Abuse (NIDA)
- National Institute of Mental Health (NIMH)
- National Heart, Lung, and Blood Institute (NHLBI)
- National Institute on Deafness and Communication Disorders (NIDCD)
- National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH) [UL1-TR001079]
- NIH Roadmap for Medical Research
- National Program of Cancer Registries at the Centers for Disease Control and Prevention (CDC) [5U58DP000795-05]
- California Department of Public Health pursuant to California Health and Safety Code Section [103885]
- CDC's National Program of Cancer Registries [5NU58DP003862-04/DP003862]
- National Cancer Institute's Surveillance, Epidemiology and End Results Program [HHSN261201000140C, HHSN261201000035C, HHSN261201000034C]
- NATIONAL CANCER INSTITUTE [P30CA016042, R01CA168482, R21CA220475] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001079] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR CHRONIC DISEASE PREV AND HEALTH PROMO [U58DP003862, U58DP000795] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [UM1AI035043, U01AI035040, U01AI035041, U01AI035042, P30AI028697, U01AI035039] Funding Source: NIH RePORTER
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Background: Chronic immune activation is a harbinger of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), yet the underlying basis is unclear. Microbial translocation, the passage of microbial components from the gastrointestinal tract into the systemic circulation, is a source of systemic immune activation in HIV infection and may be an important contributor to chronic B-cell activation and subsequent AIDS-NHL development. Method: We measured biomarkers of microbial translocation including bacterial receptors/antibodies, intestinal barrier proteins, and macrophage activation-associated cytokines/chemokines, in serum from 200 HIV-infected men from the Multicenter AIDS Cohort Study prior to their AIDS-NHL diagnosis (mean = 3.9 years; SD = 1.6 years) and 200 controls. Controls were HIV-infected men who did not develop AIDS-NHL, individually matched to cases on CD4(+) T-cell count, prior antiretroviral drug use, and recruitment year into the cohort. Results: Biomarkers of bacterial translocation and intestinal permeability were significantly increased prior to AIDS-NHL. Lipopolysaccharide-binding protein (LPB), fatty acid-binding protein 2 (FABP2), and soluble CD14 were associated with 1.6-fold, 2.9-fold, and 3.7-fold increases in AIDS-NHL risk for each unit increase on the natural log scale, respectively. Haptoglobin had a 2.1-fold increase and endotoxin-core antibody a 2.0-fold decrease risk for AIDS-NHL (fourth versus first quartile). Biomarkers of macrophage activation were significantly increased prior to AIDS-NHL: B-cell activation factor (BAFF), IL18, monocyote chemoattractant protein-1 (MCP1), tumor necrosis factor-alpha (TNF alpha), and CCL17 had 2.2-fold, 2.0-fold, 1.6-fold, 2.8-fold, and 1.7-fold increases in risk for each unit increase on the natural log scale, respectively. Conclusion: These data provide evidence for microbial translocation as a cause of the systemic immune activation in chronic HIV infection preceding AIDS-NHL development. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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