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

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 homogeneous 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.