Introduction: Younger children receiving solid organ transplantation (Tx) exhibit lower rejection rates than older individuals, likely related to immune immaturity. Standard immunosuppression protocols inadequately address individual needs and may result in avoidable adverse effects such as infection and post-transplant lymphoproliferative disorder. Thymus excision in heart Tx further alters the immune system and is associated with atopic disorders. We hypothesized that the composition of the adaptive immune system in childhood Tx is affected by age, organ, thymus excision and immunosuppression, thereby influencing the clinical outcomes of Tx.
Methods: In a national multicenter collaboration (CNTRP-POSITIVE), we included children listed for heart, lung and kidney solid organ Tx. Peripheral blood mononuclear cells (PBMC) were isolated from pre-Tx, 3-month, and 12-month post-Tx blood samples. The adaptive immune system was characterized by flow cytometric deep phenotyping and stimulation assays, grouped by stages of immune maturation (0-2, 2-<10, and 10-18 years of age).
Results: Samples were analyzed from 115 children pre-transplant, 89 at 3 months, and 69 at 12 months. Patients receiving heart or liver Tx were younger than those receiving kidneys (n = 28/36/51; median ages: 1.6/1.7/10.3 years, respectively). The CD4+ T cell count decreased significantly at 3 months post-Tx compared to pre-Tx, most pronounced in < 2 year olds (p<0.001). A recovery of CD4+ T cell levels to pre-Tx levels at 12 months was observed in kidney and liver, but not in heart recipients (p<0001). In contrast, regulatory T cells (Tregs) increased 3 months post-Tx (p= 0.0126), returning to baseline at 12 months (p= 0.8337). CD19+ B cell count remained similar post-Tx with the exception of a significant decrease at 12 months post-Tx in the < 2 years age group (p < 0001). Transitional B cells showed a decrease at 3 months post-Tx in kidney recipients, but increased in heart recipients in trend (p = 0.0584), while memory B cells changed with age but independent of immune suppression. Thymoglobulin induction therapy had profound persistent effects on T but also B cells and subpopulations while basiliximab reduced B cells but did not affect immune maturation.
Conclusion: Children receiving heart Tx showed a persistent inability to recover CD4 counts at 12 months post-Tx, unlike kidney and liver recipients, likely related to thymus excision at or before Tx. Children < 2 years show the strongest effect of Tx on CD4 T cell and CD19 B cell populations. The increase in Tregs at 3 months post-Tx across all variables supports their role in balancing an exaggerated immune response, leading to a more equilibrated state by 12 months post-Tx. Aggressive induction with Thymoglobulin results in extensive and persistent alteration of the lymphocyte composition, while basiliximab affects only B cell proportions. These findings will help to guide adaption of patient management to personalized needs.