Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma

Basile Siewe, Joey T. Pham, Mardge Cohen, Nancy A. Hessol, Alexandra Levine, Otoniel Martinez-Maza, Alan Landay

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objectives: In antiretroviral therapy (ART)-treated patients, to determine if AIDSrelated non-Hodgkin lymphoma (AIDS-NHL) is preceded by: elevated frequency of potentially malignant abnormal activated/germinal center-like B cells, elevated serum prevalence of B-cell stimulatory Toll-like receptor (TLR) ligands resulting from HIV infection-associated microbial translocation, dysregulated B-cell TLR expression/signaling, and perturbations in the frequency of immunoregulatory cells. Design: A case-control study nested with a cohort study of HIV-infected women. Methods: Prediagnostic AIDS-NHL cases (n=12, collected 1-12 months before diagnosis) and controls (n=42) from the Women's Interagency HIV Study cohort, were matched for HIV and ART status, age, race, and CD4+ lymphocyte count. Serum levels of TLR ligands, the prevalence of malignancy-associated abnormal activated/germinal center-like (CD19+CD10+CD71+CD86+AID+) B cells, TLR2 expression on B cells, expression of TLR2-modulating micro-RNA, and the frequency of regulatory T and B cells were assessed. Results: Diagnosis of AIDS-NHL was preceded by a significantly elevated frequency of activated/germinal center-like CD19+CD10+CD71+CD86+AID+ B cells (P=0.0072), elevated serum prevalence of the TLR2 ligand, and significantly elevated B-cell TLR2 expression (P=0.0015), positively correlating with the frequency of activated/germinal center-like B cells (rho=0.7273, P=0.0144). In cases, a purified subset of activated/germinal center-like B cells exhibited decreased expression of microRNAs that modulate TLR2 signaling, including miR-21, 146a, 146b, and 155. Finally, cases also exhibited significantly elevated frequencies of antitumor immunity inhibitory regulatory B cells (P=0.0024), but not regulatory T cells. Conclusions: Our findings suggest that increased microbial translocation and dysregulated TLR expression/signaling, coupled with an elevated frequency of regulatory B cells, precede the diagnosis of AIDS-NHL in HIV-infected ART-treated patients.

Original languageEnglish (US)
Pages (from-to)1659-1664
Number of pages6
JournalAIDS
Volume29
Issue number13
DOIs
StatePublished - Aug 24 2015
Externally publishedYes

Keywords

  • HIV
  • Microbial translocation
  • microRNA
  • Non-Hodgkin lymphoma
  • Regulatory B cells
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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