Epitope analysis aids in identification of donor-specific antibody against HLA-DP29 during virtual crossmatch

The use of virtual crossmatch for HLA antigen compatibility assessment before transplantation has become common practice in transplantation medicine. The accuracy of virtual crossmatch relies on accurate and complete donor HLA antigen typing and up-to-date patient HLA antigen antibody characterization. Here, we report a case in which anti-HLA-DP antibodies were detected in the patient, and the donor HLA-DPB1*29:01 was not included in the bead panel of Luminex-based single antigen bead assay (LSA).

The deceased donor HLA antigen typing results were downloaded from the United Network for Organ Sharing. Serum samples were tested for HLA antibodies using LSA. Epitope analysis was performed manually based on alignment of HLA-DP using the Sequence Alignment Tool from the IPD-IMGT/HLA database (https://www.ebi.ac.uk/ipd/imgt/hla/).

The LSA showed that anti-HLA-DP3, DP6, DP9, DP11, DP14, DP15, DP17, and DP20 were positive. HLA antigen typing with real-time polymerase chain reaction showed that the donor carried HLA-DPB1*29:01. Epitope analysis showed that the anti-HLA-DPB1*29:01 donor-specific antibody was present in this patient.

The LSA can miss antibodies against HLA antigens not represented by the beads, leading to false-negative results for donor-specific antibodies. Failure to consider the possibility of unrepresented HLA proteins may potentially lead to incorrect clinical decision. Epitope analysis may help predict reactivity to HLA antigens not present on LSA beads.