Absence Of Anti-pig Antibodies In Human Neonates And Infants: Relevance To Cardiac Xenotransplantation For Complex Congenital Abnormalities
Hara Hidetaka, David Cooper, Santiago Borasino, David Mauchley, Robert J. Dabal, Luz Padilla, David Cleveland.
University of Alabama at Birmingham, Birmingham, AL, USA.
Objective(s): Heart transplantation in neonates (<1 month-old) and infants (<1 year-old) is associated with excellent long-term survival, but is greatly limited by the critical shortage of donor hearts. Recent advances in genetic engineering and experimental xenotransplantation have provided the potential to replicate these excellent results while eliminating wait-list-associated mortality through genetically-engineered (GE) pig cardiac xenotransplantation. There are 3 known pig antigens against which humans develop ‘natural’ anti-pig antibodies, but GE pigs are now available that do not express any of these antigens (triple-knockout [TKO] pigs).
Methods: We have investigated the binding of human serum from fifty neonates (n=10) and infants (n=40) antibodies (by flow cytometry) to red blood cells (RBCs) from (i) a wild- type (WT) pig, and (ii) a TKO pig.
Results: Mean comparison of IgM and IgG binding (by relative geometric mean) to WT RBCs was 5.4 (SD 14.6) and 2.2 (SD 1.9), respectively. Thirty-six sera contained significant levels of IgM and/or IgG to WT RBCs. In contrast, IgM and IgG binding to TKO RBCs was undetectable, except in two infants. One had a very low level of IgM binding and one had very low level of IgG binding.
Conclusions: Almost all neonates and infants could receive a heart transplant from a TKO pig in the absence of any antibody binding to the graft, and thus with no (or minimal) risk of early antibody-mediated rejection. If adequate immunosuppressive therapy were administered, there is every prospect that long-term graft survival would be achieved.
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