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Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation. Out of 17 class I HLA antigens represented by >1 allele in the LABScreen single antigen bead assay, 12 had potential allele-specific reactivity. Taking advantage of our unbiased cohort of deceased donor-candidate testing (123,135 complement-dependent cytotoxicity crossmatches between 2014 and 2017), we estimated that the presence of allele-specific antibody detected using a single antigen bead assay (median fluorescence intensity, >3000) against only the rare allele was a poor predictor of a positive complement-dependent cytotoxicity crossmatch, with a positive predictive value of 0% to 7%, compared with 52.5% in allele-concordant class I HLA antibodies against A or B locus antigens. Further, we confirmed allele-specific reactivity using flow crossmatch in 3 scenarios: A11:01/A11:02, A68:01/A68:02, and B44:02/B44:03. Our results suggest that allele-specific antibodies may unnecessarily exclude transplant candidates (up to 10%) from organ offers by overcalling unacceptable antigens; incorporation of selective reactivity pattern in allocation may promote precision matching and more equitable allocation. Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.


Melissa Y Yeung, Naoka Murakami, Maria L Kafetzi, Daimon P Simmons, Isabelle Wood, Peter Macaskill, Matthew Towle, Jamie DellaGatta, Jonathan Stevens, Edward Comeau, Jane Baronas, Nabil Mohsin, Mike Chen, Jar-How Lee, William J Lane, Edgar L Milford, Indira Guleria. Impact of allele-specific anti-human leukocyte antigen class I antibodies on organ allocation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2023 Sep;23(9):1388-1400

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PMID: 37257653

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