Amino acid substitution at peptide-binding pockets of HLA class I molecules increases risk of severe acute GVHD and mortality

Date: Nov-26-2013The shift from serologic human leukocyte antigen (HLA) testing to allele-specific molecular testing was a necessary prerequisite to successful unrelated donor transplantation. However, although there is a correlation between allelic mismatch, graft-versus-host disease (GVHD), and mortality, post-transplant patient outcomes remain somewhat unpredictable.
In this week's issue of Blood, Pidala and colleagues offer new insights into the prognostic significance of specific HLA class I mismatches and their impact on patient outcome. They report that specific amino acid substitutions in the peptide binding pockets of HLA-B and -C suggest an increased risk of chronic GVHD and mortality, while mismatches at the HLA-A binding pocket have no impact.
These results offer important insights into donor choice to improve outcomes for unrelated donor stem cell transplantation.

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