Anti-Pig Antibody in Infants: Can a Genetically Engineered Pig Heart Bridge to Allotransplantation?

Abstract

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. Flow cytometry measured serum immunoglobulin M (IgM) or IgG binding to wild-type and triple-knockout 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. 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. 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.