Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Deep immunophenotyping reveals biomarkers of MIS-C in a Latin American cohort.


BACKGROUND: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after SARS-CoV-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: To characterize the immune response and clinical features of patients with acute MIS-C and determine biomarkers of disease in a cohort of 42 Latin American patients. METHODS: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and SARS-CoV-2-specific humoral and cellular response was performed using flow cytometry, ELISPOT, ELISA and neutralizing antibody assays. RESULTS: MIS-C is characterized by robust T cell activation and cytokine storm. We uncovered that while CXCL9, 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 to Kawasaki-like MIS-C. Interestingly, MIS-C patients show an NK 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. SARS-CoV2-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. CLINICAL IMPLICATIONS STATEMENT: MIS-C is distinguished by cytokine storm and decreased NK cell degranulation that is persistent after 6 months. Distinct biomarkers were identified for severe and mild forms of disease.

Authors: Rey-Jurado E, Espinosa Y, Astudillo C, Cortés LJ, Hormazabal J, Noguera L, Cofré F, Piñera C, González R, Bataszew A, Muñoz P, Benadof D, Álvarez P, Acevedo V, Vial P, Vial C, Poli MC,
Journal: J Allergy Clin Immunol; 2022 Sep 15;S0091-6749 doi:10.1016/j.jaci.2022.09.006
Year: 2022
PubMed: PMID: 36116582 (Go to PubMed)