Analysis of Plasmablasts From Children With Kawasaki Disease Reveals Evidence of a Convergent Antibody Response to a Specific Protein Epitope.

Autor:	Rowley AH; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Microbiology/Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Arrollo D; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Shulman ST; Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., Torres A; Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA., O'Brien A; Department of Microbiology and Immunology, Loyola University Stritch School of Medicine, Maywood, Illinois, USA., Wylie K; Department of Pediatrics, Washington University in St Louis, St Louis, Missouri, USA.; McDonnell Genome Institute, Washington University in St Louis, St Louis, Missouri, USA., Kim KA; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Baker SC; Department of Microbiology and Immunology, Loyola University Stritch School of Medicine, Maywood, Illinois, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2023 Aug 16; Vol. 228 (4), pp. 412-421.
DOI:	10.1093/infdis/jiad048
Abstrakt:	Background: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. Coronavirus disease 2019 (COVID-19) mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. Methods: We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. Results: We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common complementarity-determining region 3 (CDR3) motif. Conclusions: These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness. Competing Interests: Potential conflicts of interest. A. H. R, S. C. B., and S. T. S. are coinventors on provisional patent applications related to this work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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