Expression of Epstein-Barr virus latent genes and adhesion molecules in AIDS-related non-Hodgkin's 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-related NHL (ARL) have been defined: Burkitt-type NHL (BL) and polymorphic centroblastic/immunoblast-rich large cell lymphomas (CB/IB LCL). These subgroups differ in their association with the Epstein-Barr virus (EBV) and thus possibly in their pathogenesis. We studied the expression 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 molecules (LFA-1 (CD18), ICAM-1 (CD54), alpha4beta1 integrin (CD49d/CD29), L-selectin (CD62L) and CD44) was studied. We found major differences between the two subgroups. Patients with BL had significantly higher CD4-cell counts; only 40% of their lymphomas were EBV-positive, and 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-positive (79%). 58% of EBV-positive LCL (particularly those in patients with CD4-cell counts below 0.2 x 10(9)/1) had a type II or III latency phenotype. Most LCL showed expression of LFA-1, ICAM-1 and alpha4beta1 integrin. CD44s expression was restricted to CB/IB LCL, in whom high expression of the metastasis-associated exon v6-containing CD44 variant was also observed. The observed EBV-latency types and full expression of adhesion molecules suggest that defective Epstein-Barr virus immunity is important in the pathogenesis of CB/IB large cell lymphomas.
Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands.
M J
MJ
Kersten
J
J
Van Gorp
S T
ST
Pals
F
F
Boon
M H
MH
Van Oers
D018821:CD18 Antigens / Q000096:biosynthesis; D018791:CD4 Lymphocyte Count; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000096:biosynthesis; D016023:Integrins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D019041:L-Selectin / Q000096:biosynthesis; D016483:Lymphoma, AIDS-Related / Q000821:virology*; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D018960:Hyaluronan Receptors; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D014763:Viral Matrix Proteins; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin