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Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort.
Rey-Jurado, Emma; Espinosa, Yazmin; Astudillo, Camila; Jimena Cortés, Lina; Hormazabal, Juan; Noguera, Loreani P; Cofré, Fernanda; Piñera, Cecilia; González, Ricardo; Bataszew, Alexander; Muñoz Venturelli, Paula; Benadof, Dona; Álvarez, Patricia; Acevedo, Valeria; Vial, Pablo; Vial, Cecilia; Poli, M Cecilia.
  • Rey-Jurado E; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Inmunogenética y Inmunología Traslacional. Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
  • Espinosa Y; Unidad de Inmunología y Reumatología, Hospital Roberto del Río, Santiago, Chile.
  • Astudillo C; Unidad de Inmunología y Reumatología, Hospital Roberto del Río, Santiago, Chile.
  • Jimena Cortés L; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Hantavirus y Zoonosis, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
  • Hormazabal J; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Hantavirus y Zoonosis, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
  • Noguera LP; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Inmunogenética y Inmunología Traslacional. Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
  • Cofré F; Unidad de Infectología, Hospital Roberto del Río, Santiago, Chile.
  • Piñera C; Hospital Exequiel González Cortés, Santiago, Chile; Facultad de Medicina, Universidad de Chile, Santiago, Chile; Facultad de Medicina Universidad de Chile, Santiago.
  • González R; Hospital Exequiel González Cortés, Santiago, Chile.
  • Bataszew A; Unidad de Cuidados Intensivos, Hospital Roberto del Río, Santiago, Chile; Facultad de Medicina Universidad de Chile, Santiago.
  • Muñoz Venturelli P; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile.
  • Benadof D; Unidad de Infectología, Hospital Roberto del Río, Santiago, Chile; Facultad de Medicina Universidad de Chile, Santiago.
  • Álvarez P; Unidad de Inmunología y Reumatología, Hospital Roberto del Río, Santiago, Chile; Facultad de Medicina Universidad de Chile, Santiago.
  • Acevedo V; Unidad de Inmunología y Reumatología, Hospital Roberto del Río, Santiago, Chile; Facultad de Medicina Universidad de Chile, Santiago.
  • Vial P; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Hantavirus y Zoonosis, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
  • Vial C; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Hantavirus y Zoonosis, Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile.
  • Poli MC; Facultad de Medicina Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Programa de Inmunogenética y Inmunología Traslacional. Instituto de Ciencias e Innovación en Medicina, Facultad de Medicina, Universidad del Desarrollo, Santiago, Chile; Unidad de Inmunología y Reumatologí
J Allergy Clin Immunol ; 150(5): 1074-1085.e11, 2022 11.
Article in English | MEDLINE | ID: covidwho-2095539
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Child / Humans Language: English Journal: J Allergy Clin Immunol Year: 2022 Document Type: Article Affiliation country: J.jaci.2022.09.006

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Child / Humans Language: English Journal: J Allergy Clin Immunol Year: 2022 Document Type: Article Affiliation country: J.jaci.2022.09.006