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299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication occurring weeks after SARS-CoV-2 infection. The exact mechanisms leading to immune dysregulation and organ damage remain incompletely understood. Progress in understanding the immunopathology u...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751956/ http://dx.doi.org/10.1093/ofid/ofac492.377 |
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author | Zheng, Hong Yonker, Lael Donado, Michele Solomon, Ben Boribong, Brittany Gernez, Yael Maecker, Holden Sigal, Natalia Kinane, Bernard Arvin, Ann Khatri, Purvesh Weinacht, Katja |
author_facet | Zheng, Hong Yonker, Lael Donado, Michele Solomon, Ben Boribong, Brittany Gernez, Yael Maecker, Holden Sigal, Natalia Kinane, Bernard Arvin, Ann Khatri, Purvesh Weinacht, Katja |
author_sort | Zheng, Hong |
collection | PubMed |
description | BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication occurring weeks after SARS-CoV-2 infection. The exact mechanisms leading to immune dysregulation and organ damage remain incompletely understood. Progress in understanding the immunopathology underlying MIS-C has been halted by limited availability of pre-treatment patient samples and confounding effects of immunomodulatory treatment on previously studied specimens. METHODS: In this study, we have restricted enrollment to treatment-naïve patients with MIS-C and used a systems biology approach combining CyTOF, single cell transcriptomics, serum cytokine profiling and T cell receptor sequencing to dissect how immune responses in children with MIS-C differ from children with mild SARS-CoV2 infection, adults with severe COVID-19 and healthy individuals. We also integrated single cell transcriptomics datasets from post-treatment MIS-C samples to study how immune responses change along disease course. RESULTS: We identified increased activation markers and antigen presentation across multiple immune cell types in MIS-C patients from both CyTOF and single cell transcriptomics data. Importantly, in PBMCs of MIS-C patients, we identified a distinct subset of proinflammatory monocytes, with increased expression of interferon gamma response genes combined with a signature of enhanced complement expression, antigen processing and presentation, which was not observed in post-treatment MIS-C samples. Interestingly, this monocyte population bears resemblance to a subset of monocytes that emerges after the BNT162b2 mRNA vaccine booster. In addition, in PBMCs of MIS-C patients, we identify increased proportion of proliferating T/NK cells, suggesting distinct T cell expansions in MIS-C. T and NK cells in MIS-C samples also showed increased cell cytotoxicity markers. CONCLUSION: Taken together, treatment-naïve MIS-C samples display distinct monocyte clusters, activated antigen presentation and complement expression, and increased T and NK cell cytotoxicity, which may account for the clinical presentation of MIS-C. DISCLOSURES: Purvesh Khatri, PhD, Cepheid, Inc.: Advisor/Consultant|Inflammatix, Inc.: Advisor/Consultant|Inflammatix, Inc.: Inflammatix is in negotiations to license the 9-gene signature discussed here.|Inflammatix, Inc.: Stocks/Bonds. |
format | Online Article Text |
id | pubmed-9751956 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-97519562022-12-16 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome Zheng, Hong Yonker, Lael Donado, Michele Solomon, Ben Boribong, Brittany Gernez, Yael Maecker, Holden Sigal, Natalia Kinane, Bernard Arvin, Ann Khatri, Purvesh Weinacht, Katja Open Forum Infect Dis Abstracts BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a severe post-infectious complication occurring weeks after SARS-CoV-2 infection. The exact mechanisms leading to immune dysregulation and organ damage remain incompletely understood. Progress in understanding the immunopathology underlying MIS-C has been halted by limited availability of pre-treatment patient samples and confounding effects of immunomodulatory treatment on previously studied specimens. METHODS: In this study, we have restricted enrollment to treatment-naïve patients with MIS-C and used a systems biology approach combining CyTOF, single cell transcriptomics, serum cytokine profiling and T cell receptor sequencing to dissect how immune responses in children with MIS-C differ from children with mild SARS-CoV2 infection, adults with severe COVID-19 and healthy individuals. We also integrated single cell transcriptomics datasets from post-treatment MIS-C samples to study how immune responses change along disease course. RESULTS: We identified increased activation markers and antigen presentation across multiple immune cell types in MIS-C patients from both CyTOF and single cell transcriptomics data. Importantly, in PBMCs of MIS-C patients, we identified a distinct subset of proinflammatory monocytes, with increased expression of interferon gamma response genes combined with a signature of enhanced complement expression, antigen processing and presentation, which was not observed in post-treatment MIS-C samples. Interestingly, this monocyte population bears resemblance to a subset of monocytes that emerges after the BNT162b2 mRNA vaccine booster. In addition, in PBMCs of MIS-C patients, we identify increased proportion of proliferating T/NK cells, suggesting distinct T cell expansions in MIS-C. T and NK cells in MIS-C samples also showed increased cell cytotoxicity markers. CONCLUSION: Taken together, treatment-naïve MIS-C samples display distinct monocyte clusters, activated antigen presentation and complement expression, and increased T and NK cell cytotoxicity, which may account for the clinical presentation of MIS-C. DISCLOSURES: Purvesh Khatri, PhD, Cepheid, Inc.: Advisor/Consultant|Inflammatix, Inc.: Advisor/Consultant|Inflammatix, Inc.: Inflammatix is in negotiations to license the 9-gene signature discussed here.|Inflammatix, Inc.: Stocks/Bonds. Oxford University Press 2022-12-15 /pmc/articles/PMC9751956/ http://dx.doi.org/10.1093/ofid/ofac492.377 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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 reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Abstracts Zheng, Hong Yonker, Lael Donado, Michele Solomon, Ben Boribong, Brittany Gernez, Yael Maecker, Holden Sigal, Natalia Kinane, Bernard Arvin, Ann Khatri, Purvesh Weinacht, Katja 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
title | 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
title_full | 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
title_fullStr | 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
title_full_unstemmed | 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
title_short | 299. Systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
title_sort | 299. systems immunology profiling of treatment-naïve children with multisystem inflammatory syndrome |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9751956/ http://dx.doi.org/10.1093/ofid/ofac492.377 |
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