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Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Patients

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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.

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Acknowledgments

We are grateful to Infectiopole Sud for their financial support. We would also like to thank Emily Witty and Johannes Viljoen for the English review of the manuscript. This work was presented at the 6ème conférence francophone VIH/SIDA, AFRAVIH 2012 (Geneva, Switzerland, 25th to 28th of March 2012).

Conflict of interest

The authors have no financial conflict of interest.

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Authors and Affiliations

  1. INSERM U1058, Université Montpellier 1, Montpellier, France

    David Eric Ouedraogo, Nicolas Nagot, Pierre-Alain Rubbo, Karine Bollore, Vincent Foulongne, Jean-Pierre Vendrell & Edouard Tuaillon

  2. CHRU de Montpellier, Institut de Recherche en Biothérapies, Laboratoire des Cellules Circulantes Rares Humaines, Montpellier, France

    David Eric Ouedraogo, Pierre-Alain Rubbo, Karine Bollore, Jean-Pierre Vendrell & Edouard Tuaillon

  3. CHRU de Montpellier, Laboratoire de Bactériologie-Virologie, Montpellier, France

    David Eric Ouedraogo, Nils Kuster, Nicolas Nagot, Pierre-Alain Rubbo, Karine Bollore, Vincent Foulongne, Jean-Pierre Vendrell & Edouard Tuaillon

  4. Département des Maladies Infectieuses Tropicales, CHRU de Montpellier, UMI 233, Montpellier, France

    Alain Makinson & Jacques Reynes

  5. Université de la Méditerranée, IBISA Cancer Immunomonitoring Platform Institut Paoli Calmettes, Marseille, France

    Daniel Olive

  6. Département d’Hématologie, CHRU de Montpellier, Montpellier, France

    Guillaume Cartron

  7. UMR-CNRS 5235, Université Montpellier 2, Montpellier, France

    Guillaume Cartron

  8. Institute of Research in Biotherapy, CHU Montpellier Hôpital Saint-Eloi, 80, av. Augustin Fliche, 34295, Montpellier Cedex 5, France

    David Eric Ouedraogo

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  1. David Eric Ouedraogo
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  2. Alain Makinson
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  3. Nils Kuster
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Correspondence to David Eric Ouedraogo.

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Ouedraogo, D.E., Makinson, A., Kuster, N. et al. Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Patients. J Clin Immunol 33, 22–29 (2013). https://doi.org/10.1007/s10875-012-9766-0

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