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

2020; Cell Press; Volume: 183; Issue: 4 Linguagem: Inglês

10.1016/j.cell.2020.09.034

1097-4172

Conor 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, Charuta Agashe, Neha Karekar, Joanna Grabowska, Kai Nie, Jessica Le Bérichel, Hui Xie, Noam D. Beckmann, Sandeep Gangadharan, George Ofori‐Amanfo, Uri Laserson, Adeeb Rahman, Seunghee Kim‐Schulze, Alexander W. Charney, Sacha Gnjatic, Bruce D. Gelb, Miriam Mérad, Dusan Bogunovic,

COVID-19 Impact on Reproduction

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.