Thymic morphofunctionality and pediatric liver transplantation

GONZÁLEZ, FLORENCIA; BRENDA DINATALE; ITAUÁ LESTON ARAUJO,; ALEJANDRO COSTAGUTA; COSTAGUTA GUILLERMO; WILSON SAVINO,; ANA ROSA PÉREZ,

Encuentro; VI MEETING ON THYMUS TRANSCRIPTOME AND CELL BIOLOGY; 2023

In the last years, pediatric liver transplantation has become a surgery withexcellent success and limited mortality. Graft and patient survival have continuedto improve as a result of progress in immunosuppressive therapies. However,children’s thymic functional capacity and therefore, peripheral T cells repertorycould be disturbed by these therapies, and this could lead to a major incidenceof infection and graft rejection. Nowadays, there are no global reliable strategiesto evaluate thymic function after solid organ transplantation. Thus, we aimed toexplore by non-invasive techniques, how the morphology and functionality of thethymus is affected in pediatric patients undergoing immunosuppressive therapiesafter liver transplantation.During the last year, 9 pediatric patients undergoing liver transplantation wereincluded in the study (mean±SEM; 6,25±1.8 years). Blood samples werecollected previous to the transplant (pre-T), and 1, 3, 6, and 12 months after livertransplantation (post-T). Immunosuppressive protocols included calcineurininhibitors, meprednisone, and basiliximab with mycophenolate eventually addedif needed. Blood samples were assessed for recent thymic emigrants (RTEs,detected as CD4+CD45RA+CD31+ by flow cytometry) and T-cell receptorexcision circles quantification (signal-joint TRECs by qPCR). These TRECs area byproduct of TCR gene rearrangement during thymic ontogeny, so itsdetermination is a reliable method for estimating the amount of newly formed Tcells 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 266mm2, 252 mm2 1-month and 75 mm2 3-months post-T), evidencing a slightrecovery 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