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

Gruber, Conor; 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; Barcessat, Vanessa; Del Valle, Diane M.; Udondem, Samantha; Kang, Gurpawan; Gangadharan, Sandeep; Ofori-Amanfo, George; Laserson, Uri; Rahman, Adeeb; Kim-Schulze, Seunghee; Charney, Alexander; Gnjatic, Sacha; Gelb, Bruce D.; Merad, Miriam; Bogunovic, Dusan

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, CCL28). Immunophenotyping of peripheral blood revealed reductions of non-classical monocytes, and subsets of NK- and T- lymphocytes, suggesting extravasation to affected tissues. Finally, we profiled the auto-antigen reactivity of MIS-C plasma, which 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-IL6R antibody and/or IVIG, which led to rapid disease resolution.