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

Marta Epeldegui, Larry Magpantay, Yu Guo, Gordana Halec, William G. Cumberland, Priscilla K. Yen, Bernard Macatangay, Joseph Bernard Margolick, Anne Rositch, Steven Wolinsky, Otoniel Martinez-Maza, Shehnaz K. Hussain

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)945-954
Number of pages10
JournalAIDS
Volume32
Issue number7
DOIs
StatePublished - Apr 24 2018

Keywords

  • AIDS-associated non-Hodgkin lymphoma
  • HIV
  • macrophage activation
  • microbial translocation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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