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

ABSTRACT

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-Å 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/.