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Whether mismatches between donor and recipient of a kidney transplant at the HLA allele level can elicit an immune response strong enough to impact graft survival is not known.We examined the influence of HLA-DRB1 allele level mismatch on graft survival based on high-resolution typing, utilizing blood samples and clinical data provided by the Collaborative Transplant Study. HLA-DRB1*04 was selected as a model for this investigation because it is the most common HLA-DRB1 allele group and consists of several alleles with relatively high frequencies, allowing for analysis of transplants matched at the antigen level but mismatched at the allele level. Nine hundred and ninety-six recipient/donor pairs were typed for HLA-DRB1 at high resolution.No effect of HLA-DRB1*04 allele mismatch was observed in first transplants. However, in retransplants, HLA-DRB1*04 allele mismatch was associated with significantly decreased graft survival, albeit only in sensitized (PRA>5%) patients (hazard ratio 3.98, P=0.014).Our finding reinforces the concept that HLA compatibility significantly influences the outcome of kidney transplants, in sensitized retransplant recipients even at the allele level.