Defining of epitope matches and mismatches with epiTOol

Following immune challenge, specific HLA antibodies might be produced causing humoral problems such as rejection and early graft loss in organ transplants or no take in the case of platelet substitution. We already demonstrated the benefit of high-resolution HLA typing in kidney transplantation for a determination of these antibodies (Lehmann et al. doi: 10.3389/fimmu.2023.1094862). Here we present the potential use of "epiTOol", an interactive analytics tool for all-in-one processing of HLA typing and antibody data.

We analyzed a cohort of 108 living transplants regarding their antibody verified epitopes matches (EM) as well as mismatches (EMM). The recipients were 59% related and out of them 43% 1st degree related to the donor. All recipient and donors were HLA typed for HLA-A, -B, -C, -DRB1, -DRB345, -DQA1, -DQB1, -DPA1 and -DPB1 at high resolution. HLA antibody data was taken from existing routine data determined as part of quarterly screening or post-monitoring.

For HLA class I, we found unique epitopes for HLA-A (n=33), -B (n=28) and -C (n=20), with 144KR being the most frequently mismatched epitope (n=29) in our cohort. For HLA class II, the highest number of different epitopes is observed for HLA-DR (n=37), followed by -DQ (n=28) and -DP (n=13). The number of antibody-verified total EMM ranged from 0 (6 pairs) to 50 (1 pair). The largest number of EMM was observed for the DR locus (n=522), followed by A (n=440), DQ (n=418), B (n=323), C (n=217) and DP (n=213). The number of EM is not proportional to the number of EMM. The DR locus has the most matched epitopes n=1736, followed by DQ (n=1307), A (n=1183), B (n=888), C (n=798) and DP (n= 663). Finally, via epiTOol we mapped the donor specific epitopes. Interestingly, 33% (n=36) of the recipients have not formed anti-HLA antibodies following kidney transplantation although up to 40 epitope mismatches were present. In contrast, recipients with only nine EMM had produced antibodies towards the donor.

Defining epitopes is helpful for understanding the humoral response but it is not a matter of numbers but a matter of quality and could be a useful tool for donor selection in the future.

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