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Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
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Abstract
Initially, children were thought to be spared from disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a month into the epidemic, a novel multisystem inflammatory syndrome in children (MIS-C) emerged. Herein, we report on the immune profiles of nine MIS-C cases. All MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with intact neutralization capability. Cytokine profiling identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1), and mucosal immune dysregulation (IL-17A, CCL20, and CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK and T lymphocytes, suggesting extravasation to affected tissues. Finally, profiling the autoantigen reactivity of MIS-C plasma revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal, and immune-cell antigens. All patients were treated with anti-IL-6R antibody and/or IVIG, which led to rapid disease resolution.
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“MIS-C has distinct immunological features different from the two with respect to circulating cytokine profiles and composition of the T cell compartment”
From COVID-19 and the human innate immune system (2021) · cites this paper as Gruber et al., 2020
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“fever, and multi-organ dysfunction bear overlap to acute, severe COVID-19 in adults or also Kawasaki disease, a pediatric vasculitis, however, MIS-C has distinct immunological features different from the twowith respect to circulating cytokine profiles and composition of the T cell compartment (Carter et al., 2020; Co…”
Metadata
- Authors
- Gruber, C. N., Patel, R. S., Trachtman, R., Lepow, L., Amanat, F., Krammer, F., Wilson, K. M., Onel, K., Geanon, D., Tuballes, K., Patel, M., Mouskas, K., O’Donnell, T., Merritt, E., Simons, N. W., Barcessat, V., Del Valle, D. M., Udondem, S., Kang, G., Agashe, C., Karekar, N., Grabowska, J., Nie, K., Le Berichel, J., Xie, H., Beckmann, N., Gangadharan, S., Ofori-Amanfo, G., Laserson, U., Rahman, A., Kim-Schulze, S., Charney, A. W., Gnjatic, S., Gelb, B. D., Merad, M., & Bogunovic, D.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Bogunovic, Dusan
- ORCID
- Gruber, Conor N.
- Patel, Roosheel S.
- Trachtman, Rebecca
- Lepow, Lauren
- Amanat, Fatima
- Krammer, Florian
- Wilson, Karen M.
- Onel, Kenan
- Geanon, Daniel
- Tuballes, Kevin
- Patel, Manishkumar
- Mouskas, Konstantinos
- O’Donnell, Timothy
- Merritt, Elliot
- Simons, Nicole W.
- Barcessat, Vanessa
- Kang, Gurpawan
- Agashe, Charuta
- Grabowska, Joanna
- Nie, Kai
- Xie, Hui
- Beckmann, Noam
- Gangadharan, Sandeep
- Laserson, Uri
- Rahman, Adeeb
- Charney, Alexander W.
- Gnjatic, Sacha
- Gelb, Bruce D.
- Bogunovic, Dusan
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 183
- Issue
- 4
- Pages
- 982-995.e14
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7489877
- OpenAlex
- W3084924559
- Cited by
- 551
- References
- 69
- Citations by year
- 2026: 14 · 2025: 34 · 2024: 60 · 2023: 92 · 2022: 139 · 2021: 182 · 2020: 29
- FWCI
- 102.58
- Type
- journal article
- Language
- en
- Update notices
- erratum (2023-07-20)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute (CA224319, P01 CA190174, CA196521, U01 DK124165)
- National Institute of Allergy and Infectious Diseases (R01 AI127372, R21 AI129827, R21 AI134366, 5T32HD075735-07, R01 AI148963)
- National Institutes of Health
- U.S. Department of Defense (W81XWH-18-1-0528)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Kawasaki Disease and Coronary Complications
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- multisystem inflammatory syndrome in children, SARS-CoV-2, COVID-19 pandemic, systemic inflammation, antibody response, neutralizing antibodies, cytokine profiling, IL-18, interleukin-6, chemokines, non-classical monocytes, natural killer cells, T cells, autoantibodies, anti-SSB antibodies, intravenous immunoglobulin, anti-IL-6 receptor antibody
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