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antigens EBNA1, EBNA2, EBNA3A, EBNA3B and EBNA3C leader protein 
and the latent membrane proteins LMP1 and LMP2 (11). Although primary 
infection may be asymptomatic or associated with an infectious mononucleosis 
syndrome, in almost all cases the immune system controls the acute infection 
by recognizing the EBV generated antigens described above. The virus then 
persists for the life of the host in the latent state in B cells. EBV can be 
demonstrated in B lymphocytes in all positive individuals with an estimated 
frequency of 1 in 10 6 B cells. Epithelial cells provide an additional reservoir 
and in both these cell types EBV exists as a circular plasmid and expresses a 
limited set of genes. Outgrowth is prevented by immune system effector 
mechanisms including neutralizing antibodies to virus membrane proteins, 
HLA restricted EBV specific cytotoxic T cells and MHC unrestricted 
effectors. However when patients are immunosuppressed after organ 
transplants, reactivation may occur as evidence by increased viral replication 
in saliva and increased antibody titres (11,12). 
3.3 EBV Disease in Transplant Recipients 
As with other herpes viruses, reinfection with EBV is thought to result 
primarily from reactivation of latent virus. Studies have shown that there is 
increased viral replication in saliva and increased numbers of circulating EBV 
+ B cells in patients who are immunosuppressed (11). In a BMT recipient 
EBV reactivation may arise from residual host B lymphocytes which have 
survived the conditioning regimen, from donor B lymphocytes or blood 
transfusions or from oropharyngeal shedding. Disease produced by 
reactivation of EBV has until recently been less common than disease 
produced by CMV, occurring with an incidence of around 1%. However the 
increasing number of patients receiving marrow from mismatched family or 
unrelated donors has resulted in an enormously increased incidence of EBV 
lymphoproliferative disease post BMT especially in regimens employing ATG 
post transplant (13). This increase is a consequence first of the increased 
immunosuppression these patients receive and also may reflect delayed 
immune reconstitution in these patients. 
3.4 EBV Reactivation Produces Lethal Lymphoproliferation 
The incidence of EBV lymphoproliferation following BMT from an MHC 
identical sibling donor is around 0.25% (14,15). The incidence following 
mismatched or unrelated BMT ranges from 5-30% in most series with the 
highest incidence seen in patients who receive the most immunosuppressive 
regimens. 
The primary pathologic process is uncontrolled proliferation of mature B 
lymphocytes. Analysis of proliferating lymphocytes shows that these cells are 
usually of donor origin. The transformed B cells closely resemble 
morphologically and phenotypical ly the lymphoblastoid cell lines generated in 
Recombinant DNA Research, Volume 17 
