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

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

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...

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Published in:Scientific reports Vol. 10; no. 1; p. 18397
Main 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
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 27-10-2020
Nature Publishing Group
Nature Portfolio
Subjects:
631/250
631/326
692/308
692/4022
Algorithms
Alloantibodies
Antibodies, Monoclonal - immunology
Antigens
Discordance
Histocompatibility antigen HLA
HLA Antigens - chemistry
HLA Antigens - immunology
Humanities and Social Sciences
Humans
International standards
Kidney transplantation
Laboratories
Molecular Structure
multidisciplinary
Reagents
Science
Science (multidisciplinary)
Standardization
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Summary: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.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-75355-4