Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric heart recipients were associated with impairment of the immune system - a multicenter study from Sweden.

BACKGROUND

Posttransplant lymphoproliferative disorder (PTLD) is a potentially lethal complication after pediatric heart transplantation (PHT). We have previously reported an association between PTLD and (1) sternotomy during infancy, (2) mismatch concerning Epstein-Barr virus infection, (3) hypoplastic left ventricle and (4) surgically palliated congenital heart disease (CHD) as transplant indication versus cardiomyopathy (CMP). To explore whether there were significant differences in immunological profiles between the identified risk groups for PTLD and the rest of pediatric heart recipients.

METHODS

Data was partially collected as registry data from the previous study concerning PHT, PKT and HC 7. We then added clinical data and prospectively collected blood samples from additional PHT subjects from the 3 Swedish tertiary centers performing long-term follow-up after PHT. Blood samples were collected after transplantation (mean time 4.6 years, range 0.2-14.7 years) and were analyzed for immunophenotyping of T- and B-lymphocyte subpopulations and monocytes by flow cytometry, and T-cell receptor excision circles (TREC).

RESULTS

A total of 76 PHT subjects were included. Thirty-eight had undergone thymus excision during infancy and 22 had hypoplastic left ventricle. The transplant indication was CHD in 36 and CMP in 40 children. The immune profiles of the identified risk groups for PTLD were characterized by low numbers of TREC, naïve CD4+, naïve CD8+, naïve recent thymic emigrants (RTE) and among patients with CHD low numbers of T-helper cells (Th). In addition, the relative proportions of naïve cells were low.

CONCLUSIONS

The identified PTLD risk groups demonstrated significant impairment in the immune system, a pattern consistent with immune dysfunction and features of immunological aging, both of which are conditions known to increase the risk of developing PTLD.