IMMUNOREGULATORY ABNORMALITIES IN PATIENTS WITH EPSTEIN-BARR VIRUS-ASSOCIATED B-CELL LYMPHOPROLIFERATIVE DISORDERS

EBVirus-associated B cell lymphoproliferative disorder (BLPD) is a rec ognized complication of primary immunodeficiency and organ as well as bone marrow transplantation. Although the nature of the immune defects that predispose to the development of BLPD are unknown, it is postula ted that aberrant T cell responses are involved. It is our hypothesis that unbalanced lymphokine production is a major contributory factor t o abnormal B cell growth in response to EBV, resulting in BLPD. Since IFN-alpha and IL-4 are important regulators of B cell proliferation an d also regulate the synthesis of IgE, we determined serum levels of IF N-alpha, IL-4, and IgE in 8 patients with newly diagnosed BLPD. Compar ison was made to healthy recipients of organ transplants on immunosupp ressive therapy without BLPD, and normal EBV seropositive controls. Le vels of serum IL-4 were significantly elevated in both patients with B LPD as well as in healthy immunosuppressed organ transplant recipients as compared with normal healthy individuals. Patients with BLPD exhib ited a combination of significantly lower levels of serum IFN-alpha, a nd significantly higher levels of serum IgE than either healthy EBV se ropositive individuals or healthy recipients of organ transplants on i mmunosuppressive therapy. These results suggest that imbalance in the proportions of circulating cytokines favoring B cell proliferation may be contributing to the development of EBV-associated BLPD. The potent ial significance of the finding of low IFN-alpha in patients who devel op BLPD is exemplified by our recent success in the treatment of BLPD with IFN-alpha and intravenous IgG.