Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Pa
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ORIGINAL RESEARCH
Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Patients David Eric Ouedraogo & Alain Makinson & Nils Kuster & Nicolas Nagot & Pierre-Alain Rubbo & Karine Bollore & Vincent Foulongne & Guillaume Cartron & Daniel Olive & Jacques Reynes & Jean-Pierre Vendrell & Edouard Tuaillon Received: 22 May 2012 / Accepted: 9 August 2012 / Published online: 23 August 2012 # Springer Science+Business Media, LLC 2012
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.
D. E. Ouedraogo : N. Nagot : P.-A. Rubbo : K. Bollore : V. Foulongne : J.-P. Vendrell : E. Tuaillon INSERM U1058, Université Montpellier 1, Montpellier, France
D. Olive Université de la Méditerranée, IBISA Cancer Immunomonitoring Platform Institut Paoli Calmettes, Marseille, France
D. E. Ouedraogo : P.-A. Rubbo : K. Bollore : J.-P. Vendrell : E. Tuaillon CHRU de Montpellier, Institut de Recherche en Biothérapies, Laboratoire des Cellules Circulantes Rares Humaines, Montpellier, France D. E. Ouedraogo : N. Kuster : N. Nagot : P.-A. Rubbo : K. Bollore : V. Foulongne : J.-P. Vendrell : E. Tuaillon CHRU de Montpellier, Laboratoire de Bactériologie-Virologie, Montpellier, France A. Makinson : J. Reynes Département des Maladies Infectieuses Tropicales, CHRU de Montpellier, UMI 233, Montpellier, France
G. Cartron Département d’Hématologie, CHRU de Montpellier, Montpellier, France G. Cartron UMR-CNRS 5235, Université Montpellier 2, Montpellier, France D. E. Ouedraogo (*) Institute of Research in B
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