PMID- 38077376 OWN - NLM STAT- MEDLINE DCOM- 20231216 LR - 20240327 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - HLA diversity in ethnic populations can affect detection of donor-specific antibodies by single antigen beads. PG - 1287028 LID - 10.3389/fimmu.2023.1287028 [doi] LID - 1287028 AB - INTRODUCTION: In solid-organ transplantation, human leukocyte antigen (HLA) donor-specific antibodies (DSA) are strongly associated with graft rejection, graft loss, and patient death. The predominant tests used for detecting HLA DSA before and after solid-organ transplantation are HLA single antigen bead (SAB) assays. However, SAB assays may not detect antibodies directed against HLA epitopes that are not represented in the SAB. The prevalence and potential impact of unrepresented HLA epitopes are expected to vary by ethnicity, but have not been thoroughly investigated. To address this knowledge gap, HLA allele frequencies from seven ethnic populations were compared with HLA proteins present in SAB products from two manufacturers to determine unrepresented HLA proteins. MATERIALS: Allele frequencies were obtained from the Common, Intermediate, and Well Documented HLA catalog v3.0, and frequencies of unrepresented HLA types were calculated. Next-generation sequencing was used to determine HLA types of 60 deceased solid-organ donors, and results were used to determine if their HLA-A, -B, -C, and -DRB1 proteins were not present in SAB reagents from two vendors. Unrepresented HLA proteins were compared with the most similar protein in SAB assays from either vendor and then visualized using modeling software to assess potential HLA epitopes. RESULTS: For the seven ethnic populations, 0.5% to 11.8% of each population had HLA proteins not included in SAB assays from one vendor. Non-European populations had greater numbers of unrepresented alleles. Among the deceased donors, 26.7% (16/60) had at least one unrepresented HLA-A, -B, -C, or -DRB1 protein. Structural modeling demonstrated that a subset of these had potential HLA epitopes that are solvent accessible amino acid mismatches and are likely to be accessible to B cell receptors. DISCUSSION: In conclusion, SAB assays cannot completely rule out the presence of HLA DSA. HLA epitopes not represented in those assays vary by ethnicity and should not be overlooked, especially in non-European populations. Allele-level HLA typing can help determine the potential for HLA antibodies that could evade detection. CI - Copyright (c) 2023 Quon, Kaneta, Fotiadis, Menteer, Lestz, Weisert and Baxter-Lowe. FAU - Quon, Justin C AU - Quon JC AD - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Kaneta, Kelli AU - Kaneta K AD - Division of Nephrology, Children's Hospital Los Angeles, Los Angeles, CA, United States. FAU - Fotiadis, Nicholas AU - Fotiadis N AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States. FAU - Menteer, Jondavid AU - Menteer J AD - Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. AD - Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA, United States. FAU - Lestz, Rachel M AU - Lestz RM AD - Division of Nephrology, Children's Hospital Los Angeles, Los Angeles, CA, United States. AD - Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. FAU - Weisert, Molly AU - Weisert M AD - Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. AD - Division of Cardiology, Children's Hospital Los Angeles, Los Angeles, CA, United States. FAU - Baxter-Lowe, Lee Ann AU - Baxter-Lowe LA AD - Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States. AD - Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, CA, United States. LA - eng PT - Comment PT - Journal Article DEP - 20231123 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies) RN - 0 (HLA Antigens) RN - 0 (Epitopes) RN - 0 (HLA-A Antigens) SB - IM CON - HLA. 2020 Jun;95(6):516-531. PMID: 31970929 MH - Humans MH - *Ethnicity/genetics MH - *Kidney Transplantation MH - Antibodies MH - HLA Antigens MH - Tissue Donors MH - Epitopes/genetics MH - HLA-A Antigens PMC - PMC10701672 OTO - NOTNLM OT - HLA antibodies OT - HLA diversity OT - donor specific antibodies OT - race and ethnicity OT - single antigen bead assays (SAB) OT - solid organ transplantation COIS- LB-L is a member of the transplant advisory board for Luminex Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. EDAT- 2023/12/11 12:42 MHDA- 2023/12/17 13:19 PMCR- 2023/01/01 CRDT- 2023/12/11 06:29 PHST- 2023/09/01 00:00 [received] PHST- 2023/11/02 00:00 [accepted] PHST- 2023/12/17 13:19 [medline] PHST- 2023/12/11 12:42 [pubmed] PHST- 2023/12/11 06:29 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1287028 [doi] PST - epublish SO - Front Immunol. 2023 Nov 23;14:1287028. doi: 10.3389/fimmu.2023.1287028. eCollection 2023.