Patients awaiting a solid organ transplant require a histocompatibility assessment to be eligible for the national transplant waiting list (TWL). The pre-transplant testing process involves high-resolution HLA typing and regular screening of HLA antibodies using the Single Antigen Bead (SAB) assay to define the patient’s immunological profile. The SAB testing detects Unacceptable HLA antigens (UA) that are derived from previous sensitising events. The UA profile is then assigned in the OrganMatch database, which has an inbuilt matching algorithm to exclude incompatible donors expressing those UAs.
However, the antigen panel used in the SAB assay does not encompass all the HLA antigens available in the Australian donor pool. With the use of high-resolution HLA typing for deceased donor work-up in WA, there is an increased prevalence of detecting antigens that are not included in the SAB assay. Therefore, it is essential to determine whether these antigens are incompatible with patients on the waitlist to minimize the risk of presenting a high-immunological-risk offer. To address this issue, a bioinformatic pipeline was developed to predict candidate UAs that had been observed in the Australian donor pool, however, are not present in the SAB assay.
High-resolution HLA genotypes of donors in OrganMatch portal were extracted. Using this data, the pipeline identified a list of candidate UAs for each individual patient. The candidate UAs must meet the following criteria: (1) match at the first field with existing patient HLA antibody specificity above the national mean fluorescence intensity threshold of 4000, (2) share eplets or serological types with the current UAs, (3) do not share the patient’s self-eplets; or (4) be part of the exception rules (for example: DPB1*104:01 as candidate antigen for DPB1*03:01 specificity). Overall, the pipeline can determine potential high-risk antigens by utilising eplet analysis through HLA Matchmaker, HLA Epitope Registry, and the Australian donor population HLA data from the OrganMatch portal.