PROSPECTIVE ANALYSIS OF HLA IMMUNOGENICITY OF CRYOPRESERVED VALVED ALLOGRAFTS USED IN PEDIATRIC HEART-SURGERY

Background The HLA immunogenicity of cryopreserved valved allografts u sed in the surgical repair of congenital heart defects is unknown. Met hods and Results To determine the immunogenicity of these allografts, we measured prospectively the frequency of panel-reactive HLA class I alloantibodies (PRA) before, I month after, and 3 months after allogra ft implantation in 9 children (age, 5.4+/-2.1 years) and after open-he art surgery without allograft implantation in 11 age-matched control c hildren (age, 4.0+/-1.5 years). PRA was determined against an HLA-sele ct frozen T-lymphocyte panel using the antiglobulin cytotoxicity techn ique. After allograft implantation, PRA increased from 3.2+/-2.7% befo re 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 (3 3.2+/-13%) but no change at 3 months (93.0+/-3.4%), suggesting the ini tial humoral response is an IgM alloantibody that switches almost excl usively 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 sur gery, and 1.7+/-1% at 2.7+/-0.3 months after surgery. Conclusions Cryo preserved valved allografts in children induce a marked HLA alloantibo dy response that increases to broad panel reactivity within 3 months a fter surgery. This HLA sensitization has potential not only for causin g deleterious effects on allograft function but also for limiting the future opportunity of heart transplantation in patients who receive cr yopreserved valved allografts.