tetano
Editor, Senior Moderator
Cell
. 2020 Sep 14;S0092-8674(20)31231-9.
doi: 10.1016/j.cell.2020.09.034. Online ahead of print.
Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
Conor N Gruber[SUP] 1 [/SUP], Roosheel S Patel[SUP] 1 [/SUP], Rebecca Trachtman[SUP] 2 [/SUP], Lauren Lepow[SUP] 3 [/SUP], Fatima Amanat[SUP] 4 [/SUP], Florian Krammer[SUP] 4 [/SUP], Karen M Wilson[SUP] 2 [/SUP], Kenan Onel[SUP] 5 [/SUP], Daniel Geanon[SUP] 6 [/SUP], Kevin Tuballes[SUP] 6 [/SUP], Manishkumar Patel[SUP] 6 [/SUP], Konstantinos Mouskas[SUP] 3 [/SUP], Timothy O'Donnell[SUP] 3 [/SUP], Elliot Merritt[SUP] 3 [/SUP], Nicole W Simons[SUP] 3 [/SUP], Vanessa Barcessat[SUP] 6 [/SUP], Diane M Del Valle[SUP] 6 [/SUP], Samantha Udondem[SUP] 3 [/SUP], Gurpawan Kang[SUP] 3 [/SUP], Sandeep Gangadharan[SUP] 7 [/SUP], George Ofori-Amanfo[SUP] 7 [/SUP], Uri Laserson[SUP] 3 [/SUP], Adeeb Rahman[SUP] 6 [/SUP], Seunghee Kim-Schulze[SUP] 6 [/SUP], Alexander W Charney[SUP] 3 [/SUP], Sacha Gnjatic[SUP] 6 [/SUP], Bruce D Gelb[SUP] 2 [/SUP], Miriam Merad[SUP] 6 [/SUP], Dusan Bogunovic[SUP] 8 [/SUP]
Affiliations
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.
. 2020 Sep 14;S0092-8674(20)31231-9.
doi: 10.1016/j.cell.2020.09.034. Online ahead of print.
Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)
Conor N Gruber[SUP] 1 [/SUP], Roosheel S Patel[SUP] 1 [/SUP], Rebecca Trachtman[SUP] 2 [/SUP], Lauren Lepow[SUP] 3 [/SUP], Fatima Amanat[SUP] 4 [/SUP], Florian Krammer[SUP] 4 [/SUP], Karen M Wilson[SUP] 2 [/SUP], Kenan Onel[SUP] 5 [/SUP], Daniel Geanon[SUP] 6 [/SUP], Kevin Tuballes[SUP] 6 [/SUP], Manishkumar Patel[SUP] 6 [/SUP], Konstantinos Mouskas[SUP] 3 [/SUP], Timothy O'Donnell[SUP] 3 [/SUP], Elliot Merritt[SUP] 3 [/SUP], Nicole W Simons[SUP] 3 [/SUP], Vanessa Barcessat[SUP] 6 [/SUP], Diane M Del Valle[SUP] 6 [/SUP], Samantha Udondem[SUP] 3 [/SUP], Gurpawan Kang[SUP] 3 [/SUP], Sandeep Gangadharan[SUP] 7 [/SUP], George Ofori-Amanfo[SUP] 7 [/SUP], Uri Laserson[SUP] 3 [/SUP], Adeeb Rahman[SUP] 6 [/SUP], Seunghee Kim-Schulze[SUP] 6 [/SUP], Alexander W Charney[SUP] 3 [/SUP], Sacha Gnjatic[SUP] 6 [/SUP], Bruce D Gelb[SUP] 2 [/SUP], Miriam Merad[SUP] 6 [/SUP], Dusan Bogunovic[SUP] 8 [/SUP]
Affiliations
- PMID: 32991843
- PMCID: PMC7489877
- 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.