Reactivity Of Neonatal And Infant Serum To Genetically Engineered Porcine Xenografts
Kristopher B. Deatrick, Avneesh Singh, PhD, Abigail Snyder, BS, Sunjay Kaushal, MD PhD, Muhammad Mohuiddin, MD.
University of Maryland, Baltimore, MD, USA.
Objectives: The shortage of donor hearts for infants and children remains critical. Genetically engineered (GE) porcine cardiac xenografts transplanted to nonhuman primates have achieved survival of greater than 6 months. Our own laboratory is consistently producing graft survival for over a month. However, the reactivity of neonates and infants to GE pig antigens is incompletely understood. Methods: Blood was collected from 6 neonatal and infant patients and 1 adult at the time of cardiac surgery. Serum was isolated and the levels of IgM and IgG to anti non-alpha-1-3 galactose (Gal), a pig endothelial carbohydrate antigen, were tested by absorbing it on immortalized porcine aortic endothelial cells (PAECs) from (Alpha 1-3 Galactosyl transferase knockout (GTKO) pigs and cultured PAECs from Triple KO (GTKO, B4GalKO and CMAHKO) pigs and the antibody binding was evaluated using flow cytometric analysis. Results: Non-gal antibody titer, directed at either GTKO or Triple KO PAECs were only detectable in very low levels in any of our subjects (Figure 1). There were no significant differences between neonates, infants, or adults. Conclusions: Xenotransplantation is a promising avenue for expanding the potential donor pool for neonates, infants and children in need of heart transplant. Currently available organs and cells from genetic knockout pigs provoke minimal response from infants, and further studies aimed at testing the compatibility of xenotransplantation in this age group should be undertaken.
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