Deep immune profiling uncovers novel associations with clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C)

Christopher John Redmond¹, Moses M Kitakule², Aran Son³, McKella Sylvester⁴, Keith Sacco^{5

6}, Ottavia Delmonte⁷, Francesco Licciardi⁸, Riccardo Castagnoli⁷, M Cecilia Poli⁹, Yasmin Espinoza¹⁰, Camila Astudillo¹⁰, Sarah E Weber¹¹, Gina A Montealegre Sanchez¹², Karyl S Barron¹³, Mary Magliocco¹¹, Kerry Dobbs⁷, Yu Zhang¹⁴, Helen Matthews¹⁴, Cihan Oguz¹⁵, Helen C Su¹⁴, Luigi D Notarangelo⁷, Pamela Frischmeyer-Guerrerio³, Daniella M Schwartz^{3

16}

Affiliations

¹ Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA redmondchj@nih.gov.
² Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
³ Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
⁴ Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.
⁵ National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
⁶ Department of Allergy and Immunology, University of Arizona, Phoenix, Arizona, USA.
⁷ Immune Deficiency and Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁸ Dipartimento di Scienze della Sanità Pubblica e Pediatrica, Università degli Studi di Torino, Torino, Italy.
⁹ Department of Pediatrics, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
¹⁰ Hospital Roberto del Rio, Santiago, Chile.
¹¹ Molecular Development of the Immune System Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹² Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Office of the Scientific Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹⁴ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
¹⁵ Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹⁶ Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA.

PMID: 36424123
PMCID: PMC10013176
DOI: 10.1136/ard-2022-223269

Deep immune profiling uncovers novel associations with clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C)

Christopher John Redmond et al. Ann Rheum Dis. 2023 Mar.

. 2023 Mar;82(3):442-445.

doi: 10.1136/ard-2022-223269. Epub 2022 Nov 24.

Authors

Affiliations

¹ Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA redmondchj@nih.gov.
² Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA.
³ Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
⁴ Vasculitis Translational Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA.
⁵ National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
⁶ Department of Allergy and Immunology, University of Arizona, Phoenix, Arizona, USA.
⁷ Immune Deficiency and Genetics Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
⁸ Dipartimento di Scienze della Sanità Pubblica e Pediatrica, Università degli Studi di Torino, Torino, Italy.
⁹ Department of Pediatrics, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
¹⁰ Hospital Roberto del Rio, Santiago, Chile.
¹¹ Molecular Development of the Immune System Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹² Translational Autoinflammatory Diseases Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹³ Office of the Scientific Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹⁴ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
¹⁵ Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
¹⁶ Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, PA, USA.

PMID: 36424123
PMCID: PMC10013176
DOI: 10.1136/ard-2022-223269

No abstract available

Keywords: Covid-19; Immune System Diseases; Inflammation.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

Figures

**Figure 1:. Clinical associations with immunological phenotypes in MIS-C.**
A. Serum biomarkers significantly associated with clinical phenotypes in MIS-C. Biomarkers are grouped by clinical associations. Heatmap (purple) displays significance of clinical association. Heatmap (red) displays average expression level of each biomarker for the clinical group, normalized by row. B,C. Bar graphs display CD4⁺CD45RO⁺ (memory) T cell responses to SARS-CoV2 peptides in patients with oxygen requirement (B) or neurological involvement (C). PBMC were stimulated for 6h in the presence of CD28/CD49d alone or in combination with spike, membrane, or nucleocapsid peptide pools. Cytokine expression was measured using intracellular staining and flow cytometry, and the difference was calculated between CD28/CD49d + peptide-treated and CD28/CD49d-treated cells. Responses were compared in subjects with vs. without clinical symptoms. D. Bar graphs display *TRVB11* usage in MIS-C patients with vs. without Kawasaki Disease-like phenotype (MIS-C/KD), and in MIS-C/KD patients with vs. without coronary artery aneurysms. *FDR<0.05, **FDR<0.01, Mann-Whitney with multiple comparison adjustment.

See this image and copyright information in PMC

Update of

Deep immune profiling uncovers novel associations with clinical phenotypes of Multisystem Inflammatory Syndrome in Children (MIS-C).
Redmond C, Kitakule MM, Son A, Sylvester M, Sacco K, Delmonte O, Licciardi F, Castagnoli R, Poli C, Espinoza Y, Astudillo C, Weber SE, Sanchez GAM, Barron K, Magliocco M, Dobbs K, Zhang Y, Matthews H, Oguz C, Su HC, Notarangelo LD, Frischmeyer-Guerrerio PA, Schwartz DM. Redmond C, et al. medRxiv [Preprint]. 2022 Sep 2:2022.08.31.22279265. doi: 10.1101/2022.08.31.22279265. medRxiv. 2022. Update in: Ann Rheum Dis. 2023 Mar;82(3):442-445. doi: 10.1136/ard-2022-223269. PMID: 36093351 Free PMC article. Updated. Preprint.

References

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1. Sacco K, Castagnoli R, Vakkilainen S, Liu C, Delmonte OM, Oguz C, et al. Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19. Nat Med. 2022;28(5): 1050–62. - PMC - PubMed
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Deep immune profiling uncovers novel associations with clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C)

Affiliations

Deep immune profiling uncovers novel associations with clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C)

Authors

Affiliations

Conflict of interest statement

Figures

Update of

References

Publication types

MeSH terms

Supplementary concepts

Grants and funding

LinkOut - more resources

Medical