Body: A 42-year-old female was evaluated for simultaneous liver-kidney (SLK) transplant due to primary biliary cirrhosis, nonalcoholic steatohepatitis, and diabetes mellitus. At the time of evaluation, she had end-stage liver disease. Initial HLA antibody testing in November 2023 revealed Class I and II reactivity with a calculated panel reactive antibody (cPRA) of 73%, using the One Lambda single antigen bead (SAB) assay. Follow-up testing in June 2024 showed only Class I reactivity, with a reduced cPRA of 6%. The LabScreen Mixed Beads assay was negative for both Class I and II antibodies. In December 2024, a new sample tested positive for Class I reactivity on the LabScreen Mixed Beads. Reflex SAB testing identified Class I and II reactivity with a cPRA of 97.9%. The patient reported having received two blood transfusions in September 2024. An SLK offer from a DCD donor was received in January 2025 prior to listing any unacceptable antigens in UNET. Unexpectedly, the physical crossmatch, using the December 2024 sample, was T and B cell negative, despite the presence of defined donor-specific antibodies (DSA) to B35 (MFI = 12,953), Cw1 (MFI = 6,609), and Cw4 (MFI = 7,142). Surrogate crossmatches with donors expressing these antigens identified in the SAB assay were also negative indicating false positive antibody reactivity. Surprisingly, we identified nine additional false positive Class I reactivities using surrogate donor crossmatches. To further investigate, the December 2024 sample was tested externally using Werfen’s SAB assay, which confirmed Class I reactivity and a cPRA of 98%. The same false positive pattern observed in the One Lambda SAB assay was present, reinforcing the limitations of bead-based assays. The patient successfully underwent SLK transplant in January 2025. Patient is doing well post-transplant with no concern of graft rejection.
Conclusion: This case demonstrates that reliance on virtual crossmatch alone can lead to erroneous exclusion of viable organs due to false positive antibody results in the bead assay. Both One Lambda SAB and Werfen platforms yielded misleadingly high cPRA and apparent DSA, ultimately disproven by surrogate crossmatches. Physical crossmatch must remain the gold standard, particularly in patients with recent immunologic events such as transfusion, to avoid unjust organ refusal.
