Abstract
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-α (TNFα), 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.
Original language | English (US) |
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Pages (from-to) | 945-954 |
Number of pages | 10 |
Journal | AIDS |
Volume | 32 |
Issue number | 7 |
DOIs | |
State | Published - Apr 24 2018 |
Funding
Cancer incidence data were provided by the following state agencies: Maryland Cancer Registry, Center for Cancer Prevention and Control, Department of Health and Mental Hygiene, Baltimore, Maryland, USA; Illinois Department of Public Health, Illinois State Cancer Registry; Bureau of Health Statistics & Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania; Ohio Cancer Incidence Surveillance System (OCISS), Ohio Department of Health (ODH), a cancer registry partially supported in the National Program of Cancer Registries at the Centers for Disease Control and Prevention (CDC) through Cooperative Agreement # 5U58DP000795–05; and California Department of Public Health pursuant to California Health and Safety Code Section 103885; CDC’s National Program of Cancer Registries, under cooperative agreement 5NU58DP003862–04/DP003862; the National Cancer Institute’s Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute. This work was supported by grants from the National Institute of Health (NIH; P30-AI-028697, R01-CA-168482, R01-CA-168482-S) and from the UCLA AIDS Institute, UCLA Center for AIDS Research (AI28697) and the UCLA Jonsson Comprehensive Cancer Center (CA016042). This work was also supported by the Pendleton Charitable Trust and the McCarthy Family Foundation. Data/specimens utilized for the work reported in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (J.B.M.), U01-AI35042; Northwestern University (S.W.), U01-AI35039; University of California, Los Angeles (Roger Detels, O.M.-M.), U01-AI35040; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D'Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http://aidscohortstudy.org/. Cancer incidence data were provided by the following state agencies: Maryland Cancer Registry, Center for Cancer Prevention and Control, Department of Health and Mental Hygiene, Baltimore, Maryland, USA; Illinois Department of Public Health, Illinois State Cancer Registry; Bureau of Health Statistics & Research, Pennsylvania Department of Health, Harrisburg, Pennsylvania; Ohio Cancer Incidence Surveillance System (OCISS), Ohio Department of Health (ODH), a cancer registry partially supported in the National Program of Cancer Registries at the Centers for Disease Control and Prevention (CDC) through Cooperative Agreement # 5U58DP000795-05; and California Department of Public Health pursuant to California Health and Safety Code Section 103885; CDC's National Program of Cancer Registries, under cooperative agreement 5NU58DP003862-04/DP003862; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201000140C awarded to the Cancer Prevention Institute of California, contract HHSN261201000035C awarded to the University of Southern California, and contract HHSN261201000034C awarded to the Public Health Institute. Sources of support: This work was supported by grants from the National Institute of Health (NIH; P30-AI-028697, R01-CA-168482, R01-CA-168482-S) and from the UCLA AIDS Institute, UCLA Center for AIDS Research (AI28697) and the UCLA Jonsson Comprehensive Cancer Center (CA016042). This work was also supported by the Pendleton Charitable Trust and the McCarthy Family Foundation. Data/specimens utilized for the work reported in this manuscript were collected by the Multicenter AIDS Cohort Study (MACS). MACS (Principal Investigators): Johns Hopkins University Bloomberg School of Public Health (J.B.M.), U01-AI35042; Northwestern University (S.W.), U01-AI35039; University of California, Los Angeles (Roger Detels, O.M.-M.), U01-AI35040; University of Pittsburgh (Charles Rinaldo), U01-AI35041; the Center for Analysis and Management of MACS, Johns Hopkins University Bloomberg School of Public Health (Lisa Jacobson, Gypsyamber D’Souza), UM1-AI35043. The MACS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute of Mental Health (NIMH). Targeted supplemental funding for specific projects was also provided by the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute on Deafness and Communication Disorders (NIDCD). MACS data collection is also supported by UL1-TR001079 (JHU ICTR) from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH), Johns Hopkins ICTR, or NCATS. The MACS website is located at http:// aidscohortstudy.org/.
Keywords
- AIDS-associated non-Hodgkin lymphoma
- HIV
- macrophage activation
- microbial translocation
ASJC Scopus subject areas
- Infectious Diseases
- Immunology and Allergy
- Immunology