Thymic morphology and functionality are affected by immunosuppressive therapy administered after pediatric liver transplantation

GONZALEZ F; DINATALE B; LESTON ARAUJO I; SAVINO W; COSTAGUTA G; COSTAGUTA A; BOTTASSO O; PEREZ A

San Luis

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Sociedad Argentina de Inmunología

In the last years, pediatric liver transplantation has become a surgery with excellent success and limited mortality. Graft and patient survival have continued to improve as a result of progress in immunosuppressive therapies. However, children’s thymic functional capacity and therefore, peripheral T cells repertory could be disturbed by these therapies, and this could lead to a major incidence of infection and graft rejection. Nowadays, there are no global reliable strategies to evaluate thymic function after solid organ transplantation. Thus, we aimed to explore by non-invasive techniques, how the morphology and functionality of the thymus is affected in pediatric patients undergoing immunosuppressive therapies after liver transplantation. During the last year, 9 pediatric patients undergoing liver transplantation were included in the study (mean±SEM; 6,25±1.8 years). Blood samples were collected previous to the transplant (pre-T), and 1, 3, 6, and 12 months after liver transplantation (post-T). Immunosuppressive protocols included calcineurin inhibitors, meprednisone, and basiliximab with mycophenolate eventually added if needed. Blood samples were assessed for recent thymic emigrants (RTEs, detected as CD4+CD45RA+CD31+ by flow cytometry) and T-cell receptor excision circles quantification (signal-joint TRECs by qPCR). These TRECs are a byproduct of TCR gene rearrangement during thymic ontogeny, so its determination is a reliable method for estimating the amount of newly formed T cells in circulation. Thymus size was also established by ultrasonography. We found an inverse association between age and RTEs levels, but not TRECs, at any time point. Reduced thymus size was recorded, principally 1-3 monthspost-T (i.e.: in 2-age matched patients the mean of pre-T thymus volume was 266 mm2, 252 mm2 1-month and 75 mm2 3-months post-T), evidencing a slight recovery after 6-months post-T (150 mm2). RTEs levels tend to decrease in 80% of patients at 1-month post-T (%, mean±SEM, pre-T: 43.5±7.4, 1-month post-T: 38.1±11.6), and TRECs levels were significantly decreased in 5/8 patients(62.5%) at the same time point (TRECs/150.000 leukocytes, mean±SEM x103, pre-T: 14.6±4.5, 1-month post-T: 7.06±3.1, p