Director, HLA Laboratory Children's Hospital Los Angeles Los Angeles, California, United States
Abstract Text: Antibodies against donor-specific HLA proteins can cause rejection after allogeneic organ transplantation. To determine how donor ethnicity influences detection of HLA antibodies, HLA proteins in antibody detection reagents were compared with HLA allele frequencies in seven populations: European (EUR), Hispanic (HIS), Native American (NAM), African American (AFA), Asian/Pacific Islander (API), Middle Eastern/North Coast of Africa (MENA), and unknown/mixed ethnicity (UNK). For each population, HLA-A, -B, -C, and -DRB1 allele frequencies were obtained (Common, Intermediate, and Well Documented HLA Alleles catalog v3.0) and used to determine the percentage of HLA proteins in each population that are not represented in LABScreen Single Antigen reagents (OneLambda).
Based upon HLA frequency data, ethnicity influences the likelihood that an organ donor will have HLA proteins (and unique HLA epitopes) that are not represented in reagents commonly used to detect HLA antibodies (range 7.4%-34.4%). Overall, EUR had the best representation at the HLA-A, -B, -C and -DRB1 loci with 7.4%, 14.0%, 30.8%, and 8.5% of the HLA proteins missing, respectively. HLA coverage was lowest for the HIS population, with 15.5%, 28.4%, 31.6%, and 30.1% unrepresented at each respective locus. Representation of HLA-C proteins was low across all ethnicities (28.1%-34.4% unrepresented).
Commercial reagents may fail to detect clinically significant HLA antibodies due to unrepresented alleles, especially from non-European populations. The possibility of missing donor-specific antibodies should be a consideration when evaluating patients with suspected antibody-mediated rejection and in virtual crossmatching.
