Journal
ANNALS OF THORACIC SURGERY
Volume 109, Issue 4, Pages 1268-1273Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.athoracsur.2019.08.061
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Funding
- National Institutes of Health National Institute of Allergy and Infectious Diseases [AI090959]
- Children's Hospital of Alabama (Birmingham, AL)
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Background. Patients with congenital heart disease have high heart transplant waitlist mortality, and mechanical support is suboptimal. To evaluate feasibility of cardiac grafts from a genetically engineered triple-knockout pig as a bridge to allotransplantation, preformed anti-pig antibodies were measured in pediatric and adult patients. Methods. Flow cytometry measured serum immunoglobulin M (IgM) or IgG binding to wild-type and tripleknockout red blood cells (RBCs), with binding to human O-negative RBCs as a negative control. Group 1 comprise 84 pediatric patients and 64 healthy adults' sera with no previous cardiac surgery. Group 2 comprised 25 infant's sera postcardiac surgery, including 10 after palliation for hypoplastic left heart syndrome. Results. In group 1, IgM binding to wild-type RBCs occurred in 80% of sera and IgG binding occurred in in 91% of sera. Only 3% of sera showed IgM binding to triple-knockout RBCs, and 1 (<1%) was weakly positive for IgG binding. In group 2, all 25 infants demonstrated increased IgM and IgG binding to wild-type RBCs. One patient showed minimal IgM and another showed low IgG binding to triple-knockout RBCs. No infant after stage 1 Norwood demonstrated any IgG or IgM binding. Conclusions. Preformed anti-pig antibodies may not be a barrier to heart xenotransplantation in infants, even after cardiac surgery. With adequate immunosuppressive therapy, a triple-knockout pig heart transplant might function successfully as a bridge to allotransplantation.(C) 2020 by The Society of Thoracic Surgeons
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