2. Academic Validation
  3. Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

  • Cell. 2020 Nov 12;183(4):982-995.e14. doi: 10.1016/j.cell.2020.09.034.
Conor N Gruber 1,  Roosheel S Patel 1,  Rebecca Trachtman 2,  Lauren Lepow 3,  Fatima Amanat 4,  Florian Krammer 4,  Karen M Wilson 2,  Kenan Onel 5,  Daniel Geanon 6,  Kevin Tuballes 6,  Manishkumar Patel 6,  Konstantinos Mouskas 3,  Timothy O'Donnell 3,  Elliot Merritt 3,  Nicole W Simons 3,  Vanessa Barcessat 6,  Diane M Del Valle 6,  Samantha Udondem 3,  Gurpawan Kang 3,  Sandeep Gangadharan 7,  George Ofori-Amanfo 7,  Uri Laserson 3,  Adeeb Rahman 6,  Seunghee Kim-Schulze 6,  Alexander W Charney 3,  Sacha Gnjatic 6,  Bruce D Gelb 2,  Miriam Merad 6,  Dusan Bogunovic 8
Affiliations

Affiliations

  • 1 Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 2 Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 3 Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 4 Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 5 Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 6 Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 7 Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY, USA.
  • 8 Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, NY, NY, USA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, NY, NY, USA. Electronic address: dusan.bogunovic@mssm.edu.
PMID: 32991843 DOI: 10.1016/j.cell.2020.09.034
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.

Keywords

COVID-19; Kawasaki-like; MIS-C; PIMS; SARS-CoV-2; autoimmunity; dysfunction; immune; pediatrics.

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