Aims: Interferon (IFN)-gamma is a crucial regulatory cytokine in cellular immunity, and is important in immune surveillance of Epstein-Barr virus. Pathogenesis of chronic lymphocytic leukemia (CLL) is associated with an array of not completely understood disorders of cell- and humoral-mediated immunity. The aim of the study was an assessment of plasma concentration and intracellular expression of IFN-gamma, and its relationship with Epstein-Barr virus (EBV) DNA copy number, and selected clinical parameters in patients with CLL and healthy controls.

Methods: The study included samples of peripheral blood from 110 untreated patients with CLL. The control group comprised of 40 age- and sex-matched healthy individuals. The EBV-DNA copy number in peripheral blood mononuclear cells (PBMCs) was analyzed with EBV PCR kit (a single gene encoding EBV nuclear antigen 1 was amplified). The immunophenotype of PBMCs, including intracellular expression of IFN-gamma, was determined with flow cytometer. Concentration of INF-gamma in plasma was determined by ELISA.

Results: Presence of EBV DNA in PBMCs was found in 59 patients with CLL. There was a lack of detectable amounts of viral genetic material in healthy individuals. Decreased number of lymphocytes showing intracellular expression of IFN-gamma (CD3+/CD4+/IFN-gamma+ T cells, p=0.0027; CD3+/CD8+/IFN-gamma+ T cells, p=0.0044;  CD19+/IFN-gamma+ B cells, p=0.0089), and low plasma concentration (p<0.0001) of this cytokine in CLL EBV(+) patients, as compared to EBV(-) subjects and healthy controls, reflect the suppression of cell-mediated immune response and non-reactivity of lymphocytes to the studied virus. The most important factors shortening the survival of CLL patients and time to progression were: EBV-DNA copy number (>17 copies/ug DNA) and low plasma concentration of IFN-gamma (<5.25 pg/ml).

Conclusion: These data show IFN-gamma deficiency in some patients with CLL and suggest that normal T- and B-cell response is crucial for favorable prognosis in this disease.

Acknowledgments: This work was supported by research grants: NN402682440, 2011/01/N/NZ6/01762 and 2012/05/B/NZ6/00792 from State Funds for Scientific Research National Science Centre (NCN, Poland).