High Epstein-Barr virus serum load and elevated titers of anti-ZEBRA antibodies in patients with EBV-harboring tumor cells of Hodgkin's disease

Hodgkin's disease is commonly associated with EBV latent infection. The inc idence of EBV reactivation (active infection or EBV infection with replicat ive cycle) was evaluated in a series of 30 patients with untreated Hodgkin' s disease (except for one case with chronic lymphocytic leukemia) by quanti tation of EBV DNA and titration of anti-ZEBRA antibodies in serum samples. DNA was detected in serum (>2.5 x 10(2) genomes/ml) in 15 of 30 patients an d was more frequent in Hodgkin's disease with EBV-positive Reed-Sternberg c ells (10/12) than in EBV-negative cases (5/18), (P< 0.01). Of interest was the demonstration that viremia correlated well with increased titers of ant i-ZEBRA IgG and/or standard serological profiles of EBV reactivation (12/15 ), (P < 0.05). However the lack of EBV replicative cycle in Reed-Sternberg cells (negative for ZEBRA antigen and early antigen BHLF1) suggests that th e viral replication occurs in a nonneoplastic cell compartment rather than in tumor cells. The measurement of EBV DNA loads and the titration of anti- ZEBRA antibodies shed new lights on the link between activation of EBV repl ication and Hodgkin's disease: these serological markers together with the determination of the EBV status of the tumor suggest that replication of th e viral genome occurs with a decreased efficiency of the immune system, thu s allowing progression of the tumor. (C) 1999 Wiley-Liss, Inc.