EXPRESSION OF EPSTEIN-BARR-VIRUS LATENT GENES AND ADHESION MOLECULES IN AIDS-RELATED NON-HODGKINS-LYMPHOMAS - CORRELATION WITH HISTOLOGY AND CD4-CELL NUMBER

In patients with the acquired immunodeficiency syndrome, the incidence of non-Hodgkin's lymphoma is increased. Two major subgroups of AIDS-r elated NHL (ARL) have been defined: Burkitt-type NHL (BL) and polymorp hic centroblastic/immunoblast-rich large cell lymphomas (CB/IB LCL). T hese subgroups differ in their association with the Epstein-Barr virus (EBV) and thus possibly in their pathogenesis. We studied the express ion of EBER (EBV small RNA's), and EBV latent antigens LMP-1 and EBNA- 2 in 43 cases of ARL and related this to histology and immune status ( CD4-cell count). In addition, in 19 cases the expression of adhesion m olecules (LFA-1 (CD18), ICAM-1 (CD54), alpha 4 beta 1 integrin (CD49d/ CD29), L-selectin (CD62L) and CD44) was studied. We found major differ ences between the two subgroups. Patients with BL had significantly hi gher CD4-cell counts; only 40% of their lymphomas were EBV-positive, a nd when EBV-positive, were of the type I latency phenotype. Expression of adhesion molecules important for immune recognition was absent or low in all BL. In contrast, the majority of CB/IB LCL were EBER-positi ve (79%). 58% of EBV-positive LCL (particularly those in patients with CD4-cell counts below 0.2 x 10(9)/l) had a type II or III latency phe notype. Most LCL showed expression of LFA-1, ICAM-1 and alpha 4 beta 1 integrin, CD44s expression was restricted to CB/IB LCL, in whom high expression of the metastasis-associated exon v6-containing CD44 varian t was also observed. The observed EBV-latency types and full expressio n of adhesion molecules suggest that defective Epstein-Barr virus immu nity is important in the pathogenesis of CB/IB large cell lymphomas.