Absence of Antibodies in Human Neonates and Infants to Gtko/cmahko/β4galnt2ko (Triple Gene Knockout) Pig Cells: Relevance to Cardiac Xenotransplantation for Complex Congenital Heart Disease

H. Hara¹, Q. Li¹, C. A. Banks¹, T. Yamamoto¹, D. Ayares², D. C. Cleveland¹, D. K. Cooper¹

¹Surgery, University of Alabama at Birmingham, Birmingham, AL, ²Revivicor Inc., Blacksburg, VA

Meeting: 2019 American Transplant Congress

Abstract number: D85

Keywords: Antibodies, Heart, Infant, Xenoreactive antibodies

Session Information

Session Name: Poster Session D: Xenotransplantation

Session Type: Poster Session

Date: Tuesday, June 4, 2019

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall C & D

*Purpose: Heart transplantation (Tx) in neonates is associated with the best results of any organ Tx, but the lack of deceased human donor hearts in this age group limits its application. XenoTx, using genetically-engineered pigs as sources of hearts is a potential option. The aim of this study was to explore the possibility of pig heart Tx in neonates and infants.

*Methods: We measured (i) serum antibody binding in infants (n=50), children (n=20), and adults (n=64) to red blood cells (RBCs) from wild-type (WT, i.e., genetically unmodified), and triple knock-out (TKO) (i.e., not expressing of Gal, Neu5Gc, and Sda xenoantigens) pigs; (ii) anti-pig antibody levels in infants and children (n=20) who had undergone previous cardiac surgery with implantation of porcine/bovine tissue grafts, to determine whether they had become sensitized to pig antigens; and (iii) anti-pig antibodies in one infant who had undergone previous cardiac surgery and had become highly sensitized to HLA, to determine whether sensitization to pig antigens had developed.

*Results: (i) Some infants had IgM (52%) and/or IgG (76%) antibodies against WT pRBCs. All children and adults had anti-WT pig IgM/IgG antibodies. In contrast, only 2% of infants (1/50), 10% of children (2/20), and 5% of adults (3/64) had anti-TKO IgM/IgG antibodies, but the level was very low in all cases. (ii) Only 2 of 20 infants exposed previously to porcine/bovine tissue had minimal IgM/IgG to TKO pRBCs. (iii) The one highly HLA-sensitized infant had no antibodies to TKO pig antigens (or to swine leukocyte antigens).

*Conclusions: The Tx of a TKO pig heart could be carried out in most infants in the absence of anti-pig antibodies, indicating no or minimal risk of antibody-mediated rejection. Neither previous cardiac surgery (even if the patient became sensitized to HLA) nor previous exposure to porcine or bovine antigens should be detrimental to subsequent TKO pig heart Tx. A TKO pig heart could provide a successful bridge to alloTx in infants.

To cite this abstract in AMA style:

Hara H, Li Q, Banks CA, Yamamoto T, Ayares D, Cleveland DC, Cooper DK. Absence of Antibodies in Human Neonates and Infants to Gtko/cmahko/β4galnt2ko (Triple Gene Knockout) Pig Cells: Relevance to Cardiac Xenotransplantation for Complex Congenital Heart Disease [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/absence-of-antibodies-in-human-neonates-and-infants-to-gtko-cmahko-%ce%b24galnt2ko-triple-gene-knockout-pig-cells-relevance-to-cardiac-xenotransplantation-for-complex-congenital-heart-disease/. Accessed June 21, 2025.

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