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

Cell (2020-09-30)
Conor N Gruber, Roosheel S Patel, Rebecca Trachtman, Lauren Lepow, Fatima Amanat, Florian Krammer, Karen M Wilson, Kenan Onel, Daniel Geanon, Kevin Tuballes, Manishkumar Patel, Konstantinos Mouskas, Timothy O'Donnell, Elliot Merritt, Nicole W Simons, Vanessa Barcessat, Diane M Del Valle, Samantha Udondem, Gurpawan Kang, Sandeep Gangadharan, George Ofori-Amanfo, Uri Laserson, Adeeb Rahman, Seunghee Kim-Schulze, Alexander W Charney, Sacha Gnjatic, Bruce D Gelb, Miriam Merad, Dusan Bogunovic
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Human IgG (Fab specific)−Peroxidase antibody produced in goat, affinity isolated antibody
Sigma-Aldrich
Anti-Human IgA (α-chain specific)−Peroxidase antibody produced in goat, affinity isolated antibody
Sigma-Aldrich
Anti-Human IgM (μ-chain specific)−Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution