Association between Epstein-Barr virus seroconversion and immunohistochemical changes in tonsils of pediatric solid organ transplant recipients.

Objectives/hypothesis: Assess whether changes in Epstein-Barr virus (EBV) serology status relates to immunohistochemical evidence of active EBV infection in tonsillar tissue of pediatric organ transplant recipients. Children who seroconvert from EBV seronegative to seropositive status following organ transplantation are more likely to develop evidence of active EBV tonsillar infection than those who do not seroconvert. Active EBV infection is a potential early precursor of post-transplantation lymphoproliferative disorder (PTLD), a life- and/or organ-threatening disease.

Study Design: Retrospective analysis of pathology specimens and EBV serology titers of pediatric organ transplant recipients at a tertiary care academic medical center.

Methods: Immunohistochemical staining of tonsillectomy specimens and analysis of EBV serology titers were performed on 47 post-transplantation children. Eligible patients included those under age 21 years referred for tonsillectomy who had undergone solid organ transplantation. Data reviewed included gender, age at transplantation, age at tonsillectomy, interval between organ transplantation and tonsillectomy, and type of organ transplanted. EBV was detected in tonsil specimens by in situ hybridization for EBV-encoded small nuclear RNA (EBV-EBER), an indicator of active EBV infection, and EBV-encoded latent membrane protein (EBV-LMP), an indicator of latent EBV infection. Immunohistochemical staining of B-cell clonality was performed for kappa and lambda light chains. EBV serologies pre- and post-transplantation were obtained from electronic medical record data.

Results: Forty-seven children having tonsillectomy following solid organ transplantation were included. Of the 47 patients, 25 (53.5%) were EBV seronegative both before transplantation and at the time of tonsillectomy, eight (17.0%) were EBV seronegative prior to transplantation but converted to EBV seropositivity in the early (≤ 6 months) post-transplantation period, eight (17.0%) were seronegative prior to transplantation but converted to EBV seropositive in the late (≥ 6 months) post-transplantation period, and six (12.8%) were EBV seropositive prior to transplantation and remained so at the time of tonsillectomy. Overall, 20 specimens (42.6%) were positive for EBV-EBER, and three specimens (6.4%) were positive for EBV-LMP. There was significant difference in the percentage of EBV-EBER positive specimens among the four groups (P = .020). One out of eight (12.5%) of the early seroconversion group had specimens showing EBV-EBER, wheras seven out of eight (87.5%) of the late seroconversion group had tonsil specimens showing EBV-EBER (P = .005). There was no significant difference in presence of EBV-LMP among the four groups (P = .667).

Conclusions: Almost one half of post-transplantation children undergoing tonsillectomy have evidence of active EBV tonsillar infection, which was more likely in children who seroconverted from EBV-seronegative to EBV-seropositive in the late post-transplantation period than those who seroconverted in the early post-transplantation period. Based on these novel findings, continued surveillance of EBV status and adenotonsillar hypertrophy in this population should include monitoring of pretransplantation EBV status and timing of seroconversion.