EPSTEIN-BARR-VIRUS (EBV) REPLICATIVE GENE-EXPRESSION IN TUMOR-CELLS OF AIDS-RELATED NON-HODGKINS-LYMPHOMA IN RELATION TO CD4 CELL NUMBER AND ANTIBODY-TITERS TO EBV

Objective: To determine whether activation of Epstein-Barr virus (EBV) replication in tumour cells of AIDS-related non-Hodgkin's lymphoma (A RNHL) is correlated with CD4+ cell counts and influences antibody resp onse to EBV [anti-Z Epstein-Barr replicative activator (ZEBRA), anti-e arly antigen (EA), anti-viral capsid antigen (VCA)]. Design: Retrospec tive study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients a ffected by ARNHL and correlation with CD4+ cell counts and results of EBV serology (including anti-ZEBRA activity) in sera from the same pat ients. Methods: Seventeen out of 22 cases of ARNHL were selected for t he presence of EBV [Epstein-Barr early region (EBER) RNA-positive]. Im munohistochemistry was performed with anti-ZEBRA, anti-EA-restricted, anti-VCA antibodies and in situ hybridization with BHLF1/Notl oligopro bes on tumour samples. Results were statistically correlated with thos e of CD4+ cell counts (17 out of 17) and with anti-EBV antibody titres (13 out of 17) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA pr otein and synthetic peptides as antigens. Results: BZLF1 (ZEBRA) or ea rly gene products (EA-R and EA-D/BHLF1/Notl) were detected in a small proportion (<0.01-5%) of tumour cells in eight of these 17 cases by im munohistochemistry and in situ hybridization. Demonstration of replica tive gene expression did not correlate with either low CD4+ cell count s (P>0.05) or anti-EBV antibody titres (P>0.05). Anti-ZEBRA activity w as not significantly increased in patients affected with ARNHL, the ce lls of which expressed replicative gene products (P>0.05). Conclusion: The degree of immunodeficiency does not clearly enhance replicative g ene expression in tumour cells of ARNHL. EBV serology, including anti- ZEBRA activity, is not a reliable tool for predicting the occurrence o f such proliferations.