Rey, EmmaEspinosa, YazminAstudillo, CamilaJimena, LinaHormazábal, JuanNoguera, LoreaniCofré, FernandaPiñera, CeciliaGonzález, RicardoBataszew, AlexanderMuñoz, PaulaBenadof, DonaÁlvarez, PatriciaAcevedo, ValeriaVial, PabloVial, CeciliaPoli, Cecilia2023-04-262023-04-262022Rey-Jurado E, Espinosa Y, Astudillo C, Jimena Cortés L, Hormazabal J, Noguera LP, Cofré F, Piñera C, González R, Bataszew A, Muñoz Venturelli P, Benadof D, Álvarez P, Acevedo V, Vial P, Vial C, Poli MC. Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort. J Allergy Clin Immunol. 2022 Nov;150(5):1074-1085.e11. doi: 10.1016/j.jaci.2022.09.006https://repositorio.udd.cl/handle/11447/7403Background: 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.enCOVID-19NK cell deficiencyBiomarkersInflammationMultisystemic inflammatory syndrome in childrenArticlehttps://doi.org/10.1016/j.jaci.2022.09.006