Incidence and impact of allele-specific anti-HLA antibodies and high-resolution HLA genotyping on assessing immunologic compatibility

The ability to identify specific HLA molecules against which a patient has alloantibodies has revolutionized assessment of immunologic compatibility. Anti-HLA antibodies are typically evaluated as reactive against well-defined serologic antigen groups. Thus, donor HLA genotyping is aimed at defining HLA at the serologic split-antigen level to avoid incompatible antigen-antibody combinations. However, anti-HLA antibodies can have reactivities not accurately described by well-defined serologic antigens. While existence of these antibodies is acknowledged, their precise impact on clinical practice is not clear. We performed a single-center review of 2 years of pre-and post-transplant anti-HLA antibody testing data combined with high-resolution HLA genotyping data for living and deceased organ donors to evaluate the clinical impact of anti-HLA antibodies with reactivities outside of commonly defined serologic antigen groups. We find approximately 15% of patients awaiting transplantation have alloantibodies with differential reactivity for HLA proteins encoded by specific alleles within a serologic antigen group. Allele-specific antibodies are associated with positive cellular crossmatches not accurately predicted by standard donor HLA genotyping and can manifest as post-transplant donor-specific antibodies. Our data highlights the importance of evaluating anti-HLA antibodies at the allele-level and provides evidence supporting utility for high-resolution HLA genotyping in solid organ transplantation. (C) 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.