Structural epitope matching for HLA-alloimmunized thrombocytopenic patients: a new strategy to provide more effective platelet transfusion support?

BACKGROUND: During the past three decades, HLA matching for platelet (PLT) transfusion of refractory thrombocytopenic patients has been based on serologic cross-reactivity between HLA-A and HLA-B antigens. Although many blood banks are using this matching strategy, the general experience is that such matched PLT transfusions are often ineffective. STUDY DESIGN AND METHODS: This report describes a new HLA matching algorithm that considers structurally defined epitopes recognized by antibodies. HLAMatchmaker is a computer program that determines histocompatibility at the amino acid level initially designed as triplets (i.e., linear sequences of three residues in molecular surface-exposed positions) but now updated as eplets representing patches of antibody-accessible polymorphic residues surrounded by residues within a 3-angstrom radius. The eplet version of HLAMatchmaker is also useful in the analysis of HLA antibody reactivity patterns of alloimmunized patients so that acceptable mismatches can be identified. CONCLUSION: An HLA epitope-based matching protocol is proposed that may permit a more effective PLT transfusion management of refractory patients. This protocol includes high-resolution HLA-A, -B, and -C typing of patients and donors, serum screening to identify acceptable mismatches, and the identification of suitable donors in a donor database that incorporates HLAMatchmaker as a search engine. HLAMatchmaker programs can be downloaded from the Web site http://tpis.upmc.edu/tpis/HLAMatchmaker/.