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
  • 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: [email protected].
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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