Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C)
Abstract MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5–13 years) to healthy controls (n = 14, 5–15 years). Analysis was done in whole blood treated with LPS. Exp...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-43390-6 |
| _version_ | 1797559774690148352 |
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| author | Johana Isaza-Correa Laura Ryan Lynne Kelly John Allen Ashanty Melo Jennifer Jones Dean Huggard Emer Ryan Cilian Ó Maoldomhnaigh Sarah Geoghehan Patrick Gavin Timothy Ronan Leahy Karina Butler Bridget Freyne Eleanor J. Molloy |
| author_facet | Johana Isaza-Correa Laura Ryan Lynne Kelly John Allen Ashanty Melo Jennifer Jones Dean Huggard Emer Ryan Cilian Ó Maoldomhnaigh Sarah Geoghehan Patrick Gavin Timothy Ronan Leahy Karina Butler Bridget Freyne Eleanor J. Molloy |
| author_sort | Johana Isaza-Correa |
| collection | DOAJ |
| description | Abstract MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5–13 years) to healthy controls (n = 14, 5–15 years). Analysis was done in whole blood treated with LPS. Expression of CD11b and Toll-like receptor-4 (TLR4) in neutrophils and monocytes were analysed by flow cytometry. Serum cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-Ira, TNF-α, TNF-β, IFN-Υ, VEGF, EPO and GM-CSF) and mRNA levels of inflammasome molecules (NLRP3, ASC and IL-1β) were evaluated. Subpopulations of lymphocytes (CD3+, CD19+, CD56+, CD4+, CD8+, TCR Vδ1+, TCR Vδ2+) were assessed at basal levels. Absolute counts of neutrophils and NLR were high in children with MIS-C while absolute counts of lymphocytes were low. Children with MIS-C had increased levels of IL-6, IL-10, TNF-β and VEGF serum cytokines at the basal level, and significantly increased TNF-β post-LPS, compared to controls. IL-1RA and EPO decreased at baseline and post-LPS in MIS-C patients compared to controls. The percentage of CD3+ cells, NK cells and Vδ1 was lower while B cells were higher in children with MIS-C than in controls. Dysregulated immune response in children with MIS-C was evident and may be amenable to immunomodulation. |
| first_indexed | 2024-03-10T17:51:05Z |
| format | Article |
| id | doaj.art-a094ebb59af941518c948b79a03bfbfb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:51:05Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-a094ebb59af941518c948b79a03bfbfb2023-11-20T09:22:30ZengNature PortfolioScientific Reports2045-23222023-09-0113111410.1038/s41598-023-43390-6Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C)Johana Isaza-Correa0Laura Ryan1Lynne Kelly2John Allen3Ashanty Melo4Jennifer Jones5Dean Huggard6Emer Ryan7Cilian Ó Maoldomhnaigh8Sarah Geoghehan9Patrick Gavin10Timothy Ronan Leahy11Karina Butler12Bridget Freyne13Eleanor J. Molloy14Discipline of Paediatrics, Trinity College, The University of DublinDiscipline of Paediatrics, Trinity College, The University of DublinDiscipline of Paediatrics, Trinity College, The University of DublinDiscipline of Paediatrics, Trinity College, The University of DublinDiscipline of Paediatrics, Trinity College, The University of DublinInfectious Diseases/Immunology, Children’s Health Ireland at CrumlinDiscipline of Paediatrics, Trinity College, The University of DublinDiscipline of Paediatrics, Trinity College, The University of DublinInfectious Diseases/Immunology, Children’s Health Ireland at CrumlinInfectious Diseases/Immunology, Children’s Health Ireland at CrumlinInfectious Diseases/Immunology, Children’s Health Ireland at CrumlinDiscipline of Paediatrics, Trinity College, The University of DublinInfectious Diseases/Immunology, Children’s Health Ireland at CrumlinInfectious Diseases/Immunology, Children’s Health Ireland at CrumlinDiscipline of Paediatrics, Trinity College, The University of DublinAbstract MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5–13 years) to healthy controls (n = 14, 5–15 years). Analysis was done in whole blood treated with LPS. Expression of CD11b and Toll-like receptor-4 (TLR4) in neutrophils and monocytes were analysed by flow cytometry. Serum cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-Ira, TNF-α, TNF-β, IFN-Υ, VEGF, EPO and GM-CSF) and mRNA levels of inflammasome molecules (NLRP3, ASC and IL-1β) were evaluated. Subpopulations of lymphocytes (CD3+, CD19+, CD56+, CD4+, CD8+, TCR Vδ1+, TCR Vδ2+) were assessed at basal levels. Absolute counts of neutrophils and NLR were high in children with MIS-C while absolute counts of lymphocytes were low. Children with MIS-C had increased levels of IL-6, IL-10, TNF-β and VEGF serum cytokines at the basal level, and significantly increased TNF-β post-LPS, compared to controls. IL-1RA and EPO decreased at baseline and post-LPS in MIS-C patients compared to controls. The percentage of CD3+ cells, NK cells and Vδ1 was lower while B cells were higher in children with MIS-C than in controls. Dysregulated immune response in children with MIS-C was evident and may be amenable to immunomodulation.https://doi.org/10.1038/s41598-023-43390-6 |
| spellingShingle | Johana Isaza-Correa Laura Ryan Lynne Kelly John Allen Ashanty Melo Jennifer Jones Dean Huggard Emer Ryan Cilian Ó Maoldomhnaigh Sarah Geoghehan Patrick Gavin Timothy Ronan Leahy Karina Butler Bridget Freyne Eleanor J. Molloy Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C) Scientific Reports |
| title | Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C) |
| title_full | Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C) |
| title_fullStr | Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C) |
| title_full_unstemmed | Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C) |
| title_short | Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C) |
| title_sort | innate immune dysregulation in multisystem inflammatory syndrome in children mis c |
| url | https://doi.org/10.1038/s41598-023-43390-6 |
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