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


CONCLUSIONS
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.
INSERM U1058, Université Montpellier 1, Montpellier, France. daverid32@yahoo.fr
David Eric
DE
Ouedraogo
Alain
A
Makinson
Nils
N
Kuster
Nicolas
N
Nagot
Pierre-Alain
PA
Rubbo
Karine
K
Bollore
Vincent
V
Foulongne
Guillaume
G
Cartron
Daniel
D
Olive
Jacques
J
Reynes
Jean-Pierre
JP
Vendrell
Edouard
E
Tuaillon
D000328:Adult; D002051:Burkitt Lymphoma / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D015897:Comorbidity; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006689:Hodgkin Disease / Q000175:diagnosis / Q000276:immunology* / Q000821:virology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015854:Up-Regulation / Q000276:immunology*
D016207:Cytokines