Article ; Online: Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort.
The Journal of allergy and clinical immunology
2022 Volume 150, Issue 5, Page(s) 1074–1085.e11
Abstract: Background: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early ... ...
| Abstract | Background: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis; therefore, establishing clinical and laboratory biomarkers that predict complications is urgently needed. Objective: We characterized the immune response and clinical features of patients with acute MIS-C and determined biomarkers of disease in a cohort of 42 Latin American patients. Methods: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and severe acute respiratory syndrome coronavirus 2-specific humoral and cellular response was performed using flow cytometry, enzyme-linked immunospot, enzyme-linked immunosorbent assay, and neutralizing antibody assays. Results: MIS-C is characterized by robust T-cell activation and cytokine storm. We uncovered that while C-X-C motif chemokine ligand (CXCL) 9, IL-10, CXCL8, CXCL10, IL-6, and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated with KD-like MIS-C. Interestingly, MIS-C patients show a natural killer cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement, and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. Severe acute respiratory syndrome coronavirus 2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients, suggesting sustained immunity. Conclusion: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement. |
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| MeSH term(s) | Child ; Humans ; COVID-19 ; Immunophenotyping ; Latin America ; SARS-CoV-2 ; Cytokine Release Syndrome ; Antibodies, Neutralizing ; Biomarkers |
| Chemical Substances | Antibodies, Neutralizing ; Biomarkers |
| Language | English |
| Publishing date | 2022-09-15 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 121011-7 |
| ISSN | 1097-6825 ; 1085-8725 ; 0091-6749 |
| ISSN (online) | 1097-6825 ; 1085-8725 |
| ISSN | 0091-6749 |
| DOI | 10.1016/j.jaci.2022.09.006 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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