Beneficial effect of matching at the HLA-A and -B amino-acid triplet level on rejection-free clear graft survival in penetrating keratoplasy

Objective. The beneficial effect of human leukocyte antigen (HLA) matching on long-term prognosis in penetrating keratoplasty is now unequivocal but has to be weighed against the additional waiting period on an individual basis. HLAMatchmaker is a molecularly based algorithm for histocompatibility determination that can identify immunologically acceptable mismatches and thus potentially reduce time on the waiting list dramatically without negatively affecting prognosis. Methods. The HLAMatchmaker algorithm (triplet-string matching) was applied on each of 545 normal-risk keratoplasties for which complete HLA type was known at split-level resolution. Two homogenous groups were defined. Group I consisted of the 147 penetrating keratoplasties with up to 13 triplet-string mismatches (the typical upper limit of foreign in case of a single HLA-A or HLA-B allele mismatch) and was compared to the remaining 398 patients with more triplet mismatches (group II) using the Kaplan-Meier method and log-rank statistics. Analysis of clear graft survival on the basis of conventional HLA-A and HLA-B matching was performed as well. Reduction of time on the waiting list as compared to conventional HLA-A and HLA-B matching was predicted individually. Results. Triplet-string matching yielded 85% rejection-free clear graft survival 3 years after penetrating keratoplasty in group I but only 76% in group II (P<0.05), whereas conventional HLA-A and HLA-B matching did not result in any statistically significant reduction of immune reactions because of lack of statistical power (P=0.08). Triplet-string matching (13 mismatches accepted) reduces median time on the waiting list by 80%. Conclusions. Triplet-string matching seems to improve mid- to long-term prognosis in penetrating keratoplasties while simultaneously reducing time on the waiting list in most cases. It should thus be considered for histocompatibility determination in penetrating keratoplasty.