Prospective Analysis of HLA Immunogenicity of Cryopreserved Valved Allografts Used in Pediatric Heart Surgery

Abstract

BACKGROUND: The HLA immunogenicity of cryopreserved valved allografts used in the surgical repair of congenital heart defects is unknown. METHODS AND RESULTS: To determine the immunogenicity of these allografts, we measured prospectively the frequency of panel-reactive HLA class I alloantibodies (PRA) before, 1 month after, and 3 months after allograft implantation in 9 children (age, 5.4 +/- 2.1 years) and after open-heart surgery without allograft implantation in 11 age-matched control children (age, 4.0 +/- 1.5 years). PRA was determined against an HLA-select frozen T-lymphocyte panel using the antiglobulin cytotoxicity technique. After allograft implantation, PRA increased from 3.2 +/- 2.7% before surgery to 63.3 +/- 12% at 25 +/- 2 days after surgery and 99.7 +/- 0.3% at 3.4 +/- 0.3 months after surgery. The use of dithiothreitol to remove IgM alloantibodies resulted in a modest decrease in PRA at 1 month (33.2 +/- 13%) but no change at 3 months (93.0 +/- 3.4%), suggesting the initial humoral response is an IgM alloantibody that switches almost exclusively to IgG by 3 months. Control patients showed no increase in PRA over time: 1.6 +/- 1% before surgery, 3.2 +/- 1% at 28 +/- 5 days after surgery, and 1.7 +/- 1% at 2.7 +/- 0.3 months after surgery. CONCLUSIONS: Cryopreserved valved allografts in children induce a marked HLA alloantibody response that increases to broad panel reactivity within 3 months after surgery. This HLA sensitization has potential not only for causing deleterious effects on allograft function but also for limiting the future opportunity of heart transplantation in patients who receive cryopreserved valved allografts.