Food allergy after pediatric liver transplantation: role of the immature immune system and liver in oral tolerance

Food allergy (FA) after pediatric liver transplantation (LT) is a frequent problem occurring in more than 20% of patients. Symptoms are often severe with a major impact on quality of life. In-depth study of patient characteristics and literature revealed that post transplant FA is primarily associated with LT (and not so much with other solid organ transplants), young age at time of transplantation and use of tacrolimus as maintenance immunosuppression (IS).
In the first part of this study we aim to perform extensive immunological characterization of pediatric LT recipients with and without FA.
In the second part we will explore two hypotheses. The first is that the immature immune system might respond differently to tacrolimus as IS. Therefore we will study the in vitro effect of IS on human cord blood lymphocytes and intestinal explants. Secondly, we hypothesize the neontatal liver plays a crucial role in conferring tolerance to ingested antigens. To address this, we will study the development of the liver immune system in neonatal mice and its role in oral tolerance with emphasis on tolerogenic cell types in the liver.
With this study we hope to be able to recognize LT patients at risk for FA, improve our insight in the pathophysiology of LT associated FA and provide a basis for future therapeutic interventions in these patients.