Body: Here we describe the 6-year ongoing effort to find a kidney donor for a pediatric patient who became broadly sensitized against class II HLA after a liver transplant. He has completed three desensitization cycles – twice with 2 doses of IVIG and rituximab each and a third protocol involving plasmapheresis, IVIG, and 6 monthly doses of tocilizumab. Low titer antibodies were successfully reduced but high titer antibodies (≥128) targeting eplets originating from his liver donor were insufficiently changed. These eplets include 181M from DRB4*01:03, 76V from DQA1*03:03, 50R from DPA1*02:01, and 84DEAV from DPB1*11:01. Notably, this presents an opportunity to expand the donor pool by allowing inclusion of lower risk antibodies against DQB1, which was matched with the liver donor. In early 2025, the Canadian Transplant Registry introduced a Willing to Cross (WTC) program for patients with cPRA ≥99% that allows inclusion of previously unacceptable antigens in nation-wide crossmatch. These are antigens the transplant team considers to be of reduced clinical importance and when disregarded may improve the probability of transplantation. After comprehensive review of antibody and surrogate crossmatch tests to date, we chose antigens that were not repeat mismatches and where the antibody was either (1) negative in single antigen tests for the past 2 years (i.e. pre-desensitization) or (2) weak MFI in current serum, supported by low titer and negative crossmatch historically. The WTC antigen with most impact on cPRA was DQ6, which represents a low titer antibody that was responsive to desensitization (Table 1). Collectively, his cPRA was adjusted from 99.9% to 98.4%, which should accelerate finding a suitable donor within the national highly sensitized patient program.
Conclusion: Multiple lines of evidence were used to select WTC antigens, tailored to the patient’s clinical and testing history. Adoption of the new program should facilitate safe transplantation for the most difficult to match patients.
