Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146045
Title: Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation
Authors: Gu, Yue
Koh, Robynne W. K.
Lai, May Ling
Pochinco, Denise
Teo, Rachel Z. C.
Chan, Marieta
Murali, Tanusya M.
Liew, Chong Wai
Wong, Yee Hwa
Gascoigne, Nicholas R. J.
Wood, Kathryn J.
Lescar, Julien
Nickerson, Peter
MacAry, Paul A.
Vathsala, Anantharaman
Keywords: Science::Biological sciences
Issue Date: 2020
Source: Gu, Y., Koh, R. W. K., Lai, M. L., Pochinco, D., Teo, R. Z. C., Chan, M., . . . Vathsala, A. (2020). Defining the structural basis for human leukocyte antigen reactivity in clinical transplantation. Scientific Reports, 10(1), 18397-. doi:10.1038/s41598-020-75355-4
Journal: Scientific Reports
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.
URI: https://hdl.handle.net/10356/146045
ISSN: 2045-2322
DOI: 10.1038/s41598-020-75355-4
Rights: © 2020 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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