Re. Shaddy et al., PROSPECTIVE ANALYSIS OF HLA IMMUNOGENICITY OF CRYOPRESERVED VALVED ALLOGRAFTS USED IN PEDIATRIC HEART-SURGERY, Circulation, 94(5), 1996, pp. 1063-1067
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.