PMID- 35799779 OWN - NLM STAT- MEDLINE DCOM- 20220711 LR - 20220716 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - The Accuracy of Sequence-Specific Oligonucleotide and Real-Time Polymerase Chain Reaction HLA Typing in Determining the Presence of Pre-Transplant Donor-Specific Anti-HLA Antibodies and Total Eplet Mismatches for Deceased Donor Kidney Transplantation. PG - 844438 LID - 10.3389/fimmu.2022.844438 [doi] LID - 844438 AB - High resolution human leukocyte antigen (HLA) typing is important in establishing eplet compatibility and the specificity of donor-specific anti-HLA antibodies (DSA). In deceased donor kidney transplantation, high resolution donor HLA typing may not be immediately available, leading to inaccuracies during the organ allocation process. We aimed to determine the concordance and agreement of HLA-Class I and II eplet mismatches calculated using population frequency based allelic haplotype association (linkage disequilibrium, LD) from sequence-specific oligonucleotide (SSO) and real-time polymerase chain reaction (rtPCR) donor HLA typing (available at time of donor kidney allocation) compared to high-resolution Next Generation Sequencing (NGS) donor typing. NGS high resolution HLA typing were available for all recipients prior to donor kidney allocation. A cohort of 94 deceased donor-recipient pairs from a single Western Australian center were included (77 individual donors typed, 55 local and 22 interstate). The number of class I (HLA-A+B+C) and class II (HLA-DRB1+DRB3/4/5+DQB1+DQA1+DPB1+DPA1) eplet mismatches were calculated using HLAMatchmaker, comparing LD- and NGS-HLA typing. The accuracy in assigning pre-transplant DSA was compared between methods. The concordance correlation coefficient (95%CI) for HLA-class I and II eplet mismatches were 0.994 (0.992 to 0.996) and 0.991 (0.986 to 0.993), respectively. The 95% limits of agreement for class I were -1.3 (-1.6 to -1.1) to 1.4 (1.2 to 1.7) and -4.8 (-5.7 to -3.9) to 5.0 (4.1 to 5.9) for Class II. Disagreement between the two methods were present for 11 and 37 of the Class I and II donor/recipient pairs. Of which, 5 had a difference of >/=5 class II eplet mismatches. There were 34 (36%) recipients with potential pre-transplant DSA, of which 8 (24% of recipients with DSA) had indeterminate and ultimately false positive DSA assigned by donor LD-typing. While the concordance between NGS- and LD-typing was high, the limits of agreement suggest meaningful differences between these two techniques. The inaccurate assignment of DSA from donor LD-typing may result in associated HLA being considered unacceptable mismatches, inappropriately precluding candidates' access to transplantation. Accurate imputation of two-field HLA alleles based on LD from SSO and rtPCR HLA typing remains a substantial challenge in clinical practice in-lieu of widely available, rapid, high-resolution methods. CI - Copyright (c) 2022 Larkins, D'Orsogna, Taverniti, Sharma, Chakera, Chan, Krishnan, Wong and Lim. FAU - Larkins, Nicholas G AU - Larkins NG AD - Department of Nephrology, Perth Children's Hospital, Perth, WA, Australia. AD - School of Medicine, University of Western Australia, Perth, WA, Australia. FAU - D'Orsogna, Lloyd AU - D'Orsogna L AD - Department of Clinical Immunology, Fiona Stanley Hospital, Perth, WA, Australia. FAU - Taverniti, Anne AU - Taverniti A AD - Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia. FAU - Sharma, Ankit AU - Sharma A AD - Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia. AD - Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia. AD - Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, NSW, Australia. FAU - Chakera, Aron AU - Chakera A AD - Department of Renal Medicine, Sir Charles Gardiner Hospital, Perth, WA, Australia. FAU - Chan, Doris AU - Chan D AD - Department of Renal Medicine, Sir Charles Gardiner Hospital, Perth, WA, Australia. FAU - Krishnan, Anoushka AU - Krishnan A AD - Department of Renal Medicine, Royal Perth Hospital, Perth, WA, Australia. FAU - Wong, Germaine AU - Wong G AD - Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, NSW, Australia. AD - Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia. AD - Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, NSW, Australia. FAU - Lim, Wai H AU - Lim WH AD - School of Medicine, University of Western Australia, Perth, WA, Australia. AD - Department of Renal Medicine, Sir Charles Gardiner Hospital, Perth, WA, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220620 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Oligonucleotides) SB - IM MH - Australia MH - Histocompatibility Testing/methods MH - Humans MH - Kidney MH - *Kidney Transplantation/adverse effects MH - Oligonucleotides MH - Real-Time Polymerase Chain Reaction MH - Tissue Donors PMC - PMC9253866 OTO - NOTNLM OT - epitopes OT - genotyping techniques OT - histocompatibility OT - histocompatibility typing OT - kidney transplantation OT - organ transplantation COIS- The 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. EDAT- 2022/07/09 06:00 MHDA- 2022/07/12 06:00 PMCR- 2022/01/01 CRDT- 2022/07/08 02:37 PHST- 2021/12/28 00:00 [received] PHST- 2022/05/18 00:00 [accepted] PHST- 2022/07/08 02:37 [entrez] PHST- 2022/07/09 06:00 [pubmed] PHST- 2022/07/12 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.844438 [doi] PST - epublish SO - Front Immunol. 2022 Jun 20;13:844438. doi: 10.3389/fimmu.2022.844438. eCollection 2022.