Increased T-cell activation and Th1 cytokine concentrations prior to the diagnosis of B-cell lymphoma in HIV infected patients

J Clin Immunol. 2013 Jan;33(1):22-9. doi: 10.1007/s10875-012-9766-0. Epub 2012 Aug 23.

Abstract

Background: Despite the use of combined antiretroviral therapy, HIV-infected individuals have a higher risk of developing B-cell lymphoma compared to the general population. We aim to explore whether lymphocyte activation, increase in Th1 response as well as markers of EBV reactivation, may precede lymphoma diagnosis.

Methods: Thirteen cases and 26 controls matched on CD4(+) T-cell count and HIV plasma viral load were identified. Samples were collected 0 to 5 years prior to B-cell lymphoma diagnosis. Seven out of 13 (54 %) and 16/26 (61.5 %) of cases and controls were receiving antiretroviral therapy at the time of sampling, respectively. CD8(+) T-cell activation and Th1 cytokine concentrations were measured before lymphoma onset, together with IgG antibodies directed against viral capsid antigen (VCA) and serum levels of EBV DNA.

Results: A higher level of CD8(+) T-cell activation was observed in patients developing lymphoma. Four out of seven Th1 cytokine serum concentrations were significantly higher in patients with lymphoma than in the control group: IL-2R, IL-12p40/70, IFN-γ-inducible protein 10 (IP-10) and monokine induced by IFN-γ (MIG). Anti-VCA IgG level were significantly higher in cases than in controls. Four cases (30 %) but no controls had detectable EBV DNA in serum.

Conclusion: A higher level of T-cell activation, Th1 cytokine serum concentration and markers of EBV replication, preceded B-cell lymphoma diagnosis. This may suggest that viral antigen stimulation is associated with the genesis of lymphoma in HIV-infected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Burkitt Lymphoma / diagnosis
  • Burkitt Lymphoma / immunology*
  • Burkitt Lymphoma / virology
  • Case-Control Studies
  • Comorbidity
  • Cytokines / biosynthesis
  • Cytokines / metabolism*
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • HIV Infections / pathology
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology
  • Hodgkin Disease / diagnosis
  • Hodgkin Disease / immunology*
  • Hodgkin Disease / virology
  • Humans
  • Lymphocyte Activation / immunology*
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / virology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / virology*
  • Up-Regulation / immunology*

Substances

  • Cytokines