"THE SAB GAP": Incomplete HLA allele representation in Single Antigen Bead assays and its implications for surrogate...

Single Antigen Bead (SAB) assays are widely used for anti-HLA antibodies detection and virtual crossmatch. Their interpretation assumes that omission of specific HLA alleles can be adequately compensated through representation of shared epitopes on related alleles included within the panel.

This study retrospectively examined 535 Indian donor-recipient pairs to pinpoint HLA alleles missing from two commercial SAB panels. We analyzed the antibody-verified eplet repertoires of unrepresented alleles using HLAMatchmaker and the HLA Epitope Registry and evaluated the extent to which these repertoires were represented through surrogate alleles included within the SAB panels.

At least one unrepresented allele was identified in 35.8% of cases. A total of 77 unique alleles were absent across both panels, including 32 missing alleles from both. Approximately 70% of unrepresented alleles carried antibody-verified eplets, and over 80% demonstrated high or intermediate exposition. Although many antibody-verified eplets were represented through related alleles contained within the SAB panels, the extent of surrogate structural representation varied across recurrent donor alleles.

Incomplete allele representation in SAB panels may limit the completeness of surrogate epitope-level representation associated with recurrent donor alleles, even when individual antibody-verified eplets remain represented through related alleles. These findings highlight a structural limitation in current SAB design and support incorporation of epitope-level analysis to refine immunological risk assessment. In this study, the term 'SAB GAP' refers to the potential disconnect between allele level representation and the completeness of surrogate structural representation of antibody-verified eplet repertoires within commercial SAB panels.