Expression of Epstein–Barr Virus Transformation–Associated Genes in Tissues of Patients with EBV Lymphoproliferative Disease

Epstein–Barr virus (EBV) has been associated with serious or fatal lymphoproliferative disease in immunocompromised patients. EBV nuclear protein 2 and latent membrane protein are characteristically expressed in B lymphocytes proliferating in vitro in response to growth transformation by EBV. These two proteins are thought to be effectors of lymphocyte growth since they increase the expression of B-lymphocyte activation (CD23) and cell-adhesion (LFA 3 and ICAM 1) molecules in vitro. Using monoclonal antibody–immune microscopy, we have demonstrated that these two EBV proteins and their associated B-lymphocyte activation or adhesion molecules are expressed in the infiltrating B lymphocytes in immunocompromised patients with EBV lymphoproliferative disease. These monoclonal antibodies should be useful in the early diagnosis of EBV lymphoproliferative disease and in distinguishing it from other B-lymphocyte cancers associated with EBV, such as Burkitt's lymphoma. The finding of EBV nuclear protein 2 and latent membrane protein and their associated activation or adhesion molecules provides a further pathophysiologic link between EBV and the proliferation of B lymphocytes in immunocompromised patients. (N Engl J Med 1989; 321:1080–5.) THE proliferation of B lymphocytes infected with Epstein–Barr virus (EBV) can result in serious or fatal disease in immunocompromised recipients of kidney, heart, liver, thymus, or allogeneic bone marrow transplants. 1 2 3 4 5 6 Lymph nodes or other tissues may be infiltrated by monoclonal, oligoclonal, or polyclonal EBV-infected, immature B lymphocytes. These lymphocytes contain EBV DNA and stain positively for EBV nuclear proteins with the use of EBV-immune human serum samples. The cells are latently infected, but the expression of specific EBV proteins has not been documented. In contrast to the paucity of information about the expression of EBV proteins in human tissues, six . . .