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HLAmatchmaker: a molecularly based algorithm for histocompatibility determination. IV. An alternative strategy to increase the number of compatible donors for highly sensitized patients.

Rene J Duquesnoy·Judy Howe·Steve Takemoto
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Abstract

BACKGROUND: HLAMatchmaker is a computer algorithm that determines human leukocyte antigen (HLA) compatibility at the level of polymorphic amino acid triplets in antibody-accessible sequence positions. Recent studies have shown that HLA-DR-matched kidney transplant recipients with zero to two triplet mismatches had almost identical graft survival rates as those with zero HLA-A,B,DR antigen mismatches. This report describes how HLAMatchmaker can be used to identify more compatible donors for highly sensitized patients. METHODS: The HLAMatchmaker program was used to calculate the probability of finding a donor (PFD) with zero, one, or two triplet mismatches for 54 highly sensitized patients waiting for a kidney transplant and having panel reactive antibody (PRA) values greater than 85% and 50 randomly selected nonsensitized patients with PRA values less than 3%. RESULTS: There was a wide variability for PFD values for the two patient cohorts. If only donors with zero HLA-A,B mismatches were deemed acceptable for recipients, the median PFD of a zero-antigen mismatch was 0.046% for nonsensitized patients and 0.009% for highly sensitized patients (P=0.007). Half of the highly sensitized patients had a PFD below 0.01%, or fewer than 1 in 10,000 donors would have zero antigen mismatches. Application of HLAMatchmaker identified additional HLA antigens with zero-triplet mismatches for 27 patients, resulting in a 1.8-fold increase in PFD. Considering additional antigens with one-triplet or two-triplet mismatches increased the PFD by an additional 3.8-fold and 13.7-fold, respectively. Acceptable antigen mismatches for 37 of the 54 highly sensitized patients were identified by consistently negative reactions in serum screens, and their addition resulted in a 12.7-fold increase of the PFD to a median of 0.141%. Applying these acceptable antigens to the HLAMatchmaker algorithm identified additional antigens with zero or acceptable triplet mismatches and their inclusion increased the PFD by 3.3-fold to 0.347%. CONCLUSIONS: HLAMatchmaker offers a valuable strategy for identifying more suitably HLA-matched donors and has the potential for alleviating the problem of accumulation of highly sensitized patients on the transplant waiting list.

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AlgorithmsAmino Acid SequenceAutoantibodiesDatabases, FactualGraft SurvivalHLA-A AntigensHLA-B AntigensHistocompatibility TestingHumansMolecular Sequence DataTissue DonorsTissue and Organ ProcurementJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Rene J Duquesnoy, Judy Howe, Steve Takemoto. 2003-03-27. HLAmatchmaker: a molecularly based algorithm for histocompatibility determination. IV. An alternative strategy to increase the number of compatible donors for highly sensitized patients.. https://doi.org/10.1097/01.tp.0000055097.58209.83

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