VIRAL AND IMMUNOLOGICAL ASPECTS OF EPSTEIN-BARR-VIRUS INFECTION IN PEDIATRIC LIVER-TRANSPLANT RECIPIENTS

Pediatric allograft recipients in particular are at increased risk for Epstein-Barr virus (EBV)-associated disorders, Early identification a nd diagnosis of EBV-associated disorders is critical, since disease pr ogression can often be halted by reduction of immunosuppression. In th is study we examined viral and immunologic parameters of EBV infection in the circulation of pediatric liver recipients to identify factors associated with disease, Peripheral blood DNA from pediatric liver rec ipients was analyzed by PCR for the EBV genes coding for the nuclear a ntigen 1 (EBNA-1) and the viral capsid antigen gp220, Sequences for th ese viral genes could be readily detected in the circulation of 36.5% of patients, Moreover, identification of the EBV genome was associated with symptomatic infection, suggesting that circulating EBV may be a useful marker of disease, Since EBV-infected B cells release the low-a ffinity IgE receptor (sCD23), we measured sCD23 in the circulation of pediatric liver recipients and found it to be elevated in patients wit h detectable virus or symptoms of infection, However, sCD23 was also e levated in cases where no EBV was detectable, suggesting that factors other than viral infection could stimulate release of sCD23, To furthe r characterize the immune response to EBV infection, the peripheral le vels of IL-4, IL-5, IL-10, and IFN-gamma were determined in pediatric liver recipients, Each of these cytokines was elevated in patients wit h symptoms or circulating virus compared with stable, age-matched live r recipients, IL-4, in particular, was significantly increased, indica ting an important role for this cytokine in EBV infection. Together, t hese findings suggest that (1) monitoring circulating levels of EBV ma y be useful in patients at high risk and (2) cytokines that promote B cell growth and differentiation contribute to EBV-associated disorders .