Benchmarking and Automating Single Antigen Bead Interpretation for Histocompatibility Assessment

This project produces 2 key deliverables:The field's first HLA antibody reference standard in the form of a benchmark containing ground truth across well-vetted HLA antibody cases, ranging in complexity, that can be used to measure the performance of single antigen bead interpretation methods for HLA antibody identification and virtual crossmatchAn automated single antigen bead interpretation algorithm that goes beyond MFI thresholds for antibody identification and virtual crossmatch. The algorithm is rule-based, and the reasoning behind each result can be traced.This project directly responds to the 2005 OPTN/UNOS challenge to the histocompatibility community to achieve uniform HLA antibody characterization due to the known variation in the interpretation of single antigen bead (SAB) data between HLA centers, which has these 2 major impacts:Inequitable transplant access. What one center uses as an MFI threshold for unacceptable antigen listing differs from what another center uses. The same patient's SAB data may deem a donor incompatible at one center, but compatible at another.Inequitable transplant outcomes. Transplant outcomes are impacted by each center's interpretation of the clinical significance of an antibody in cases where highly sensitized patients have no choice but a DSA-positive transplant. The center-to-center variation in SAB data interpretation obscures multi-center DSA outcome study findings. This impedes the establishment of outcome-validated DSA-positive transplant guidelines.A planned multi-center DSA outcome study involves the analysis of raw SAB data from 11 US HLA centers, which will utilize the automated SAB data interpretation algorithm that has shown near perfect concordance with the HLA antibody benchmark's ground truth.Explore the benchmark and algorithm: https://hlabassist.app