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Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH)
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, th...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Academy of Allergy, Asthma & Immunology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923010/ https://www.ncbi.nlm.nih.gov/pubmed/35304157 http://dx.doi.org/10.1016/j.jaci.2022.02.028 |
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author | Kumar, Deepak Rostad, Christina A. Jaggi, Preeti Villacis Nunez, D. Sofia Prince, Chengyu Lu, Austin Hussaini, Laila Nguyen, Thinh H. Malik, Sakshi Ponder, Lori A. Shenoy, Sreekala P.V. Anderson, Evan J. Briones, Michael Sanz, Ignacio Prahalad, Sampath Chandrakasan, Shanmuganathan |
author_facet | Kumar, Deepak Rostad, Christina A. Jaggi, Preeti Villacis Nunez, D. Sofia Prince, Chengyu Lu, Austin Hussaini, Laila Nguyen, Thinh H. Malik, Sakshi Ponder, Lori A. Shenoy, Sreekala P.V. Anderson, Evan J. Briones, Michael Sanz, Ignacio Prahalad, Sampath Chandrakasan, Shanmuganathan |
author_sort | Kumar, Deepak |
collection | PubMed |
description | BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from that of well-characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: We sought to compare the qualitative and quantitative inflammatory profile differences between patients with MIS-C, coronavirus disease 2019, and HLH. METHODS: Clinical data abstraction from patient charts, T-cell immunophenotyping, and multiplex cytokine and chemokine profiling were performed for patients with MIS-C, patients with coronavirus disease 2019, and patients with HLH. RESULTS: We found that both patients with MIS-C and patients with HLH showed robust T-cell activation, markers of senescence, and exhaustion along with elevated T(H)1 and proinflammatory cytokines such as IFN-γ, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10. In comparison, the amplitude of T-cell activation and the levels of cytokines/chemokines were higher in patients with HLH when compared with patients with MIS-C. Distinguishing inflammatory features of MIS-C included elevation in T(H)2 inflammatory cytokines such as IL-4 and IL-13 and cytokine mediators of angiogenesis, vascular injury, and tissue repair such as vascular endothelial growth factor A and platelet-derived growth factor. Immune activation and hypercytokinemia in MIS-C resolved at follow-up. In addition, when these immune parameters were correlated with clinical parameters, CD8(+) T-cell activation correlated with cardiac dysfunction parameters such as B-type natriuretic peptide and troponin and inversely correlated with platelet count. CONCLUSIONS: Overall, this study characterizes unique and overlapping immunologic features that help to define the hyperinflammation associated with MIS-C versus HLH. |
format | Online Article Text |
id | pubmed-8923010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Academy of Allergy, Asthma & Immunology |
record_format | MEDLINE/PubMed |
spelling | pubmed-89230102022-03-15 Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) Kumar, Deepak Rostad, Christina A. Jaggi, Preeti Villacis Nunez, D. Sofia Prince, Chengyu Lu, Austin Hussaini, Laila Nguyen, Thinh H. Malik, Sakshi Ponder, Lori A. Shenoy, Sreekala P.V. Anderson, Evan J. Briones, Michael Sanz, Ignacio Prahalad, Sampath Chandrakasan, Shanmuganathan J Allergy Clin Immunol Covid-19 BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is a potentially life-threatening sequela of severe acute respiratory syndrome coronavirus 2 infection characterized by hyperinflammation and multiorgan dysfunction. Although hyperinflammation is a prominent manifestation of MIS-C, there is limited understanding of how the inflammatory state of MIS-C differs from that of well-characterized hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis (HLH). OBJECTIVES: We sought to compare the qualitative and quantitative inflammatory profile differences between patients with MIS-C, coronavirus disease 2019, and HLH. METHODS: Clinical data abstraction from patient charts, T-cell immunophenotyping, and multiplex cytokine and chemokine profiling were performed for patients with MIS-C, patients with coronavirus disease 2019, and patients with HLH. RESULTS: We found that both patients with MIS-C and patients with HLH showed robust T-cell activation, markers of senescence, and exhaustion along with elevated T(H)1 and proinflammatory cytokines such as IFN-γ, C-X-C motif chemokine ligand 9, and C-X-C motif chemokine ligand 10. In comparison, the amplitude of T-cell activation and the levels of cytokines/chemokines were higher in patients with HLH when compared with patients with MIS-C. Distinguishing inflammatory features of MIS-C included elevation in T(H)2 inflammatory cytokines such as IL-4 and IL-13 and cytokine mediators of angiogenesis, vascular injury, and tissue repair such as vascular endothelial growth factor A and platelet-derived growth factor. Immune activation and hypercytokinemia in MIS-C resolved at follow-up. In addition, when these immune parameters were correlated with clinical parameters, CD8(+) T-cell activation correlated with cardiac dysfunction parameters such as B-type natriuretic peptide and troponin and inversely correlated with platelet count. CONCLUSIONS: Overall, this study characterizes unique and overlapping immunologic features that help to define the hyperinflammation associated with MIS-C versus HLH. American Academy of Allergy, Asthma & Immunology 2022-05 2022-03-15 /pmc/articles/PMC8923010/ /pubmed/35304157 http://dx.doi.org/10.1016/j.jaci.2022.02.028 Text en © 2022 American Academy of Allergy, Asthma & Immunology. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Covid-19 Kumar, Deepak Rostad, Christina A. Jaggi, Preeti Villacis Nunez, D. Sofia Prince, Chengyu Lu, Austin Hussaini, Laila Nguyen, Thinh H. Malik, Sakshi Ponder, Lori A. Shenoy, Sreekala P.V. Anderson, Evan J. Briones, Michael Sanz, Ignacio Prahalad, Sampath Chandrakasan, Shanmuganathan Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) |
title | Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) |
title_full | Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) |
title_fullStr | Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) |
title_full_unstemmed | Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) |
title_short | Distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (MIS-C) versus hemophagocytic lymphohistiocytosis (HLH) |
title_sort | distinguishing immune activation and inflammatory signatures of multisystem inflammatory syndrome in children (mis-c) versus hemophagocytic lymphohistiocytosis (hlh) |
topic | Covid-19 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923010/ https://www.ncbi.nlm.nih.gov/pubmed/35304157 http://dx.doi.org/10.1016/j.jaci.2022.02.028 |
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