Donor selection in pediatric kidney transplantation using DR and DQ eplet mismatching: A new histocompatibility paradigm.

Abstract

It is now appreciated that more HLA-DR mismatching at the time of the first renal transplant is associated with higher degrees of sensitization, lower rates and longer times to retransplantation, and worse graft outcomes in children who are subsequently retransplanted. As such, our pediatric renal transplant program preferentially uses 0 or 1 HLA-DR-mismatched kidneys and reserves 2 DR-mismatched kidneys for recipients with an eminent need for a kidney. Based on a new HLA class II epitope matching strategy that is designed to minimize dnDSA production to DR and DQ antigens, we evaluated the prevalence of DR and DQ eplet mismatching for dd offers made to our pediatric wait-listed candidates. Each candidate/dd pair were HLA-DR (β1 and β3 and/or β5) and DQ (α1 and β1) allele typed by rSSO and were then evaluated for eplet mismatches by the HLAMatchmaker program. We evaluated 78 offers made to 16 children on our UNOS waiting list from 27 consecutive dd from 4/14/14 to 3/23/15. The data show that 40% (8/20) of the 1 DR-mismatched dd offers and 64% (37/58) of the 2 DR-mismatched offers were in the high-risk category for both DR and DQ dnDSA development. Whereas only 15% (3/20) of the 1 DR-mismatched offers and 5% (3/58) of the 2 DR-mismatched offers were in the low-risk category for both DR and DQ dnDSA development, 55% and 33% of the 1 DR- and 2 DR-mismatched offers, respectively, had a favorable DQ eplet mismatch threshold. In summary, HLA class II eplet mismatching is common in potential pediatric transplant recipient/donor pairs. Additional study will be necessary to validate the DR and DQ eplet threshold levels in children and to determine whether eplet mismatching strategies in donor selection result in improved transplant outcome and decreased dnDSA production.