Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation

Abstract The current state-of-the-art technology employed to assess anti-human leukocyte antigen antibodies (Anti-HLA Ab) for donor-recipient matching and patient risk stratification in renal transplantation is the single antigen bead (SAB) assay. However, there are limitations to the SAB assay as i...

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Autores principales:	Yue Gu, Robynne W. K. Koh, May Ling Lai, Denise Pochinco, Rachel Z. C. Teo, Marieta Chan, Tanusya M. Murali, Chong Wai Liew, Yee Hwa Wong, Nicholas R. J. Gascoigne, Kathryn J. Wood, Julien Lescar, Peter Nickerson, Paul A. MacAry, Anantharaman Vathsala
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d892bb6ce394324a9db08fda50ac687
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spelling	oai:doaj.org-article:0d892bb6ce394324a9db08fda50ac6872021-12-02T15:09:56ZDefining the structural basis for human leukocyte antigen reactivity in clinical transplantation10.1038/s41598-020-75355-42045-2322https://doaj.org/article/0d892bb6ce394324a9db08fda50ac6872020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-75355-4https://doaj.org/toc/2045-2322Abstract The current state-of-the-art technology employed to assess anti-human leukocyte antigen antibodies (Anti-HLA Ab) for donor-recipient matching and patient risk stratification in renal transplantation is the single antigen bead (SAB) assay. However, there are limitations to the SAB assay as it is not quantitative and due to variations in techniques and reagents, there is no standardization across laboratories. In this study, a structurally-defined human monoclonal alloantibody was employed to provide a mechanistic explanation for how fundamental alloantibody biology influences the readout from the SAB assay. Performance of the clinical SAB assay was evaluated by altering Anti-HLA Ab concentration, subclass, and detection reagents. Tests were conducted in parallel by two internationally accredited laboratories using standardized protocols and reagents. We show that alloantibody concentration, subclass, laboratory-specific detection devices, subclass-specific detection reagents all contribute to a significant degree of variation in the readout. We report a significant prozone effect affecting HLA alleles that are bound strongly by the test alloantibody as opposed to those bound weakly and this phenomenon is independent of complement. These data highlight the importance for establishing international standards for SAB assay calibration and have significant implications for our understanding of discordance in previous studies that have analyzed its clinical relevance.Yue GuRobynne W. K. KohMay Ling LaiDenise PochincoRachel Z. C. TeoMarieta ChanTanusya M. MuraliChong Wai LiewYee Hwa WongNicholas R. J. GascoigneKathryn J. WoodJulien LescarPeter NickersonPaul A. MacAryAnantharaman VathsalaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yue Gu Robynne W. K. Koh May Ling Lai Denise Pochinco Rachel Z. C. Teo Marieta Chan Tanusya M. Murali Chong Wai Liew Yee Hwa Wong Nicholas R. J. Gascoigne Kathryn J. Wood Julien Lescar Peter Nickerson Paul A. MacAry Anantharaman Vathsala Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
description	Abstract The current state-of-the-art technology employed to assess anti-human leukocyte antigen antibodies (Anti-HLA Ab) for donor-recipient matching and patient risk stratification in renal transplantation is the single antigen bead (SAB) assay. However, there are limitations to the SAB assay as it is not quantitative and due to variations in techniques and reagents, there is no standardization across laboratories. In this study, a structurally-defined human monoclonal alloantibody was employed to provide a mechanistic explanation for how fundamental alloantibody biology influences the readout from the SAB assay. Performance of the clinical SAB assay was evaluated by altering Anti-HLA Ab concentration, subclass, and detection reagents. Tests were conducted in parallel by two internationally accredited laboratories using standardized protocols and reagents. We show that alloantibody concentration, subclass, laboratory-specific detection devices, subclass-specific detection reagents all contribute to a significant degree of variation in the readout. We report a significant prozone effect affecting HLA alleles that are bound strongly by the test alloantibody as opposed to those bound weakly and this phenomenon is independent of complement. These data highlight the importance for establishing international standards for SAB assay calibration and have significant implications for our understanding of discordance in previous studies that have analyzed its clinical relevance.
format	article
author	Yue Gu Robynne W. K. Koh May Ling Lai Denise Pochinco Rachel Z. C. Teo Marieta Chan Tanusya M. Murali Chong Wai Liew Yee Hwa Wong Nicholas R. J. Gascoigne Kathryn J. Wood Julien Lescar Peter Nickerson Paul A. MacAry Anantharaman Vathsala
author_facet	Yue Gu Robynne W. K. Koh May Ling Lai Denise Pochinco Rachel Z. C. Teo Marieta Chan Tanusya M. Murali Chong Wai Liew Yee Hwa Wong Nicholas R. J. Gascoigne Kathryn J. Wood Julien Lescar Peter Nickerson Paul A. MacAry Anantharaman Vathsala
author_sort	Yue Gu
title	Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
title_short	Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
title_full	Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
title_fullStr	Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
title_full_unstemmed	Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
title_sort	defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/0d892bb6ce394324a9db08fda50ac687
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Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation

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