Near absence of IL-15R-alpha T-cells in EBV-associated Hodgkin lymphoma patients

Abstract

8087 Background: Epstein-Barr virus (EBV) (+) Hodgkin's lymphoma (HL) has been linked to acute infectious mononucleosis (AIM). EBV-associated AIM was recently reported (Sauce et al, Blood 2006, 108: 11) to be associated with a long lasting immunologic scar (near complete absence of IL-15 receptor alpha (IL-15Ra expression on T cells in peripheral blood mononuclear cells (PBMC)). We sought to confirm the scar observation and to determine whether such a scar might also be characteristic of EBV (+) HL patients. Methods: PBMCs from 5 donors with history of AIM (3 months to 4 years before), 10 EBV-seropositive donors without history of AIM, 10 EBV-seronegative donors, 22 HL patients with EBV (+) tumors and 29 HL patients with EBV (-) tumors were assayed to determine IL-15Ra expression on CD3/CD8+ cells using a FACScalibur flow cytometer. Results: IL-15Ra expression in healthy donors with history of AIM [mean: 2.9% (1.5–6.5%)] was much lower than in those without history of AIM [mean: 83% (65–98%)] (p = 0.001). Expression did not differ between healthy EBV-seropositive donors without history of AIM [mean: 82% (65–95%)] and healthy EBV-seronegative donors [mean: 89% (82–98%)] (p = 0.32). Expression was markedly different between EBV (-) HL [mean: 82% (72–99%)] and EBV (+) HL patients [mean: 3.2% (1.1–7.1%)] [p = 0.001, 95% CI(10.3–32.1)]. No difference was found when age, time blood was drawn (pre or post-treatment), disease stage and histological subtype were compared. This IL- 15Ra deficit was seen in patients before and more than one year after standard therapy. Conclusions: This study confirms the virtual absence of IL-15Ra expression in lymphocytes from patients with history of AIM. That observation is now extended to include patients with EBV (+) HL at presentation and in remission. Whether this deficit contributes to the pathogenesis of EBV (+) associated HL remains to be determined. No significant financial relationships to disclose.