Pediatric Liver Transplant Recipients with Food Allergy Show Profound T-cell Activation and Elevated Inflammatory Cytokines

Pediatric liver transplantation (LT) significantly improves survival for end-stage liver disease, but recipients face unique post-transplant complications. One such challenge is an increased susceptibility to food allergy, termed liver transplantation-associated food allergy (LTFA), whose underlying immune mechanisms remain poorly understood. Current understanding of post-transplant immune dysregulation often focuses on preventing rejection, yet less is known about its role in allergic sensitization. Identifying specific immune profiles could offer insights into LTFA pathogenesis and potential therapeutic targets beyond standard immunosuppression.

This cross-sectional cohort study evaluated circulating T- and B-cell subsets and serum cytokine profiles in 43 pediatric LT recipients, of whom 8 had LTFA. For comparison, nontransplanted food allergic controls and healthy controls were also recruited. T- and B-lymphocyte subsets were analyzed using flow cytometry, while serum concentrations of 15 cytokines were measured. The primary objective was to identify distinct immune signatures associated with LTFA development in this vulnerable population.

Children diagnosed with LTFA exhibited significantly increased proportions of newly activated CD69+ T cells within both CD4+ and CD8+ subsets (P = 0.001 and P < 0.001, respectively), compared to LT recipients without LTFA. They also showed a higher proportion of CD4+ T cells with the effector memory CD45RA+ phenotype (P = 0.001). Furthermore, LTFA patients had elevated serum levels of the T helper 2 cytokine interleukin-4 (P = 0.004) and the pro-inflammatory cytokines tumor necrosis factor-alpha (P = 0.007) and tumor necrosis factor-beta (P = 0.03). This broad immune activation was not observed in the nontransplanted food allergic control group, suggesting a transplant-specific immune context.

Notably, the entire cohort of LT recipients, irrespective of food allergy status, displayed significantly larger proportions of activated, memory, effector, and effector memory CD45RA+ subsets of both CD4+ and CD8+ T cells, alongside higher levels of all 15 measured cytokines, when compared to age- and sex-matched healthy controls.