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Distorted TCR repertoires define multisystem inflammatory syndrome in children
While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood....
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612519/ https://www.ncbi.nlm.nih.gov/pubmed/36301874 http://dx.doi.org/10.1371/journal.pone.0274289 |
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author | Malik, Amna Tóth, Eszter N. Teng, Michelle S. Hurst, Jacob Watt, Eleanor Wise, Lauren Kent, Natalie Bartram, Jack Grandjean, Louis Dominguez-Villar, Margarita Adams, Stuart Cooper, Nichola |
author_facet | Malik, Amna Tóth, Eszter N. Teng, Michelle S. Hurst, Jacob Watt, Eleanor Wise, Lauren Kent, Natalie Bartram, Jack Grandjean, Louis Dominguez-Villar, Margarita Adams, Stuart Cooper, Nichola |
author_sort | Malik, Amna |
collection | PubMed |
description | While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with MIS-C (n = 12) and mild (n = 8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n = 8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of children with MIS-C are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines MIS-C in children. |
format | Online Article Text |
id | pubmed-9612519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-96125192022-10-28 Distorted TCR repertoires define multisystem inflammatory syndrome in children Malik, Amna Tóth, Eszter N. Teng, Michelle S. Hurst, Jacob Watt, Eleanor Wise, Lauren Kent, Natalie Bartram, Jack Grandjean, Louis Dominguez-Villar, Margarita Adams, Stuart Cooper, Nichola PLoS One Research Article While the majority of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) display mild or no symptoms, rare individuals develop severe disease presenting with multisystem inflammatory syndrome (MIS-C). The reason for variable clinical manifestations is not understood. Here, we carried out TCR sequencing and conducted comparative analyses of TCR repertoires between children with MIS-C (n = 12) and mild (n = 8) COVID-19. We compared these repertoires with unexposed individuals (samples collected pre-COVID-19 pandemic: n = 8) and with the Adaptive Biotechnologies MIRA dataset, which includes over 135,000 high-confidence SARS-CoV-2-specific TCRs. We show that the repertoires of children with MIS-C are characterised by the expansion of TRBV11-2 chains with high junctional and CDR3 diversity. Moreover, the CDR3 sequences of TRBV11-2 clones shift away from SARS-CoV-2 specific T cell clones, resulting in distorted TCR repertoires. In conclusion, our study reports that CDR3-independent expansion of TRBV11-2+ cells, lacking SARS-CoV-2 specificity, defines MIS-C in children. Public Library of Science 2022-10-27 /pmc/articles/PMC9612519/ /pubmed/36301874 http://dx.doi.org/10.1371/journal.pone.0274289 Text en © 2022 Malik et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Malik, Amna Tóth, Eszter N. Teng, Michelle S. Hurst, Jacob Watt, Eleanor Wise, Lauren Kent, Natalie Bartram, Jack Grandjean, Louis Dominguez-Villar, Margarita Adams, Stuart Cooper, Nichola Distorted TCR repertoires define multisystem inflammatory syndrome in children |
title | Distorted TCR repertoires define multisystem inflammatory syndrome in children |
title_full | Distorted TCR repertoires define multisystem inflammatory syndrome in children |
title_fullStr | Distorted TCR repertoires define multisystem inflammatory syndrome in children |
title_full_unstemmed | Distorted TCR repertoires define multisystem inflammatory syndrome in children |
title_short | Distorted TCR repertoires define multisystem inflammatory syndrome in children |
title_sort | distorted tcr repertoires define multisystem inflammatory syndrome in children |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9612519/ https://www.ncbi.nlm.nih.gov/pubmed/36301874 http://dx.doi.org/10.1371/journal.pone.0274289 |
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