title: HLAMatchmaker-driven analysis of responses to HLA-typed platelet transfusions in alloimmunized thrombocytopenic patients.
abstract: This study describes a novel application of HLAMatchmaker to determine platelet compatibility in 16 alloimmunized patients with aplastic anemia refractory to random donor platelet transfusions. HLAMatchmaker is a software algorithm that predicts HLA compatibility by identifying immunogenic epitopes represented by amino acid triplets in antibody-accessible regions of human leukocyte antigen (HLA) molecules and determines the number of triplet mismatches (TMMs) and highly immunogenic triplet mismatches (HIMMs). Corrected count increments (CCIs) and molecular HLA typing were available for 523 transfusions. Conventional compatibility assessment based on cross-reactive group (CREG) determination was not predictive of transfusion outcome. Low HIMMs and TMMs numbers were associated with a higher likelihood of satisfactory (CCIs > or = 8) compared with unsatisfactory (CCIs < 8) outcomes (median HIMMs = 4 vs 6, p2 value < .001; median TMMs = 11 vs 13, p2 value < .001). Although receiver operator characteristic curves revealed that HIMMs or TMMs number are not powerful predictors of individual transfusion outcome, a threshold of at least 3 HIMMs or at least 9 TMMs appeared to be associated with successful transfusions. Triplet-matched transfusions were successful, regardless of CREG matching. Our data validate HLAMatchmaker for platelet transfusions and demonstrate its potential to refine and expand donor selection for HLA-alloimmunized patients.
authors.affiliation: Department of Transfusion Medicine, Bldg 10, 1C711, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Ashok
authors.initials: A
authors.lastname: Nambiar
authors.forename: Rene J
authors.initials: RJ
authors.lastname: Duquesnoy
authors.forename: Sharon
authors.initials: S
authors.lastname: Adams
authors.forename: Yingdong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jaime
authors.initials: J
authors.lastname: Oblitas
authors.forename: Susan
authors.initials: S
authors.lastname: Leitman
authors.forename: David
authors.initials: D
authors.lastname: Stroncek
authors.forename: Francesco
authors.initials: F
authors.lastname: Marincola
mesh_terms: D003429:Cross Reactions; D006680:HLA Antigens; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D017713:Platelet Transfusion / Q000009:adverse effects / Q000379:methods*; D013921:Thrombocytopenia / Q000097:blood / Q000276:immunology* / Q000628:therapy*
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D007519:Isoantigens