Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
Cell, 2020
Gruber C., Patel R., Trachtman R., Lepow L., Amanat F., Krammer F., Wilson K., Onel K., Geanon D., Tuballes K., Patel M., Mouskas K., O’Donnell T., Merritt E., Simons N., Barcessat V., Del Valle D., Udondem S., Kang G., Agashe C., Karekar N., Grabowska J., Nie K., Le Berichel J., Xie H., Beckmann N., Gangadharan S., Ofori-Amanfo G., Laserson U., Rahman A., Kim-Schulze S., Charney A., Gnjatic S., Gelb B., Merad M., Bogunovic D.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
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.