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A prospective study of serum microbial translocation biomarkers and risk of AIDS-related non-Hodgkin lymphoma.


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-? (TNF?), 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.

SUBMITTER: Epeldegui M 

PROVIDER: S-EPMC5869109 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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A prospective study of serum microbial translocation biomarkers and risk of AIDS-related non-Hodgkin lymphoma.

Epeldegui Marta M   Magpantay Larry L   Guo Yu Y   Halec Gordana G   Cumberland William G WG   Yen Priscilla K PK   Macatangay Bernard B   Margolick Joseph B JB   Rositch Anne F AF   Wolinsky Steven S   Martinez-Maza Otoniel O   Hussain Shehnaz K SK  

AIDS (London, England) 20180401 7


<h4>Background</h4>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.<h4>Method</h4>We measured biomarkers of microbial translocation in  ...[more]

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