Immunosuppression after pediatric liver transplantation may lead to early and prolonged acute thymic involution: findings from a pilot longitudinal study.

Thymopoiesis plays a critical role in shaping the peripheral T-cell repertoire during childhood. Following pediatric liver transplantation, patients receive intensive immunosuppressive therapy, which may disrupt thymic function; however, thymic involvement after solid organ transplantation remains poorly understood. This prospective study aimed to assess the impact of immunosuppressive therapy on thymic function and morphology in pediatric first-time liver transplant recipients over a one-year follow-up period. The primary endpoint was thymic output, quantified by sjTRECs. Secondary endpoints included intrathymic proliferation (sj/βTREC ratio), recent thymic emigrants (RTEs; CD3+CD4+CD45RA+CD31+), and thymic morphology. All parameters were assessed at baseline (pre-transplant) and at 1, 3, 6, and 12 months post-transplantation. Twelve patients were included. The primary endpoint -thymic output measured by sjTRECs- declined significantly over the 12-month follow-up (β=-732.1, p<0.01). Among secondary endpoints, the sj/βTREC ratio, showed a significant reduction after 3 months post-transplant. The frequency of recent thymic emigrants (RTEs) showed a decreasing trend that did not reach statistical significance, although RTEs correlated positively with sjTREC levels. Thymic size assessed by ultrasound decreased significantly at 3 months, with partial recovery thereafter. Taken together, our findings provide preliminary evidence of early and persistent changes in markers of thymic function following immunosuppression after pediatric liver transplantation. Although the small sample size and exploratory design of this pilot study warrant cautious interpretation, the statistically significant changes observed in the primary endpoint justify the need for further controlled studies to better characterize the impact of immunosuppressive therapy on thymic recovery and long-term immune reconstitution in pediatric transplant recipients.