CoChat
Sign Up
Cited by 94Down syndrome and intellectual disability researchImmunodeficiency and Autoimmune DisordersImmune Response and Inflammation

Increased systemic inflammation in children with Down syndrome

Huggard, Dean, Kelly, Lynne, Ryan, Emer, McGrane, Fiona, Lagan, Niamh, Roche, Edna, Balfe, Joanne, Leahy, T. Ronan +3 more·2020·Cytokine
DOI 10.1016/j.cyto.2019.154938
Open this paper in CoChat — free account

Abstract

Children with Down syndrome (DS) develop more infections, have an increased mortality from sepsis and an increased incidence of chronic inflammatory conditions. Cytokine dysregulation may underpin these clinical sequelae and raised pro-inflammatory biomarkers are a feature in adults with DS. The importance of the anti-inflammatory mediators IL-1ra and IL-10, as well as cytokines Epo and VEGF, which could impact on the pathogenesis and outcomes in congenital heart disease (CHD) which is more prevalent in DS, are less well known. We examined a comprehensive array of pro-(IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ), and anti-inflammatory (IL-10 and IL-1ra) mediators, cytokines involved in inflammation in response to hypoxia (EPO), propagating angiogenesis (VEGF), and myelopoiesis (GM-CSF), by enzyme linked immunosorbent assay (ELISA), as well as discussing the potential impact of significant CHD and Lipopolysaccharide endotoxin on these mediators. 114 children with DS and 60 age and sex matched controls were recruited. Children with Down syndrome exhibit significantly greater levels of pro and anti-inflammatory cytokines; IL-2, IL-6, IL-10, IL-1ra, as well as increased Epo, VEGF and GM-CSF at baseline. CHD does not seem to have an impact on circulating cytokines beyond the acute surgical phase. Both cohorts had similar responses to LPS stimulation. These differences may contribute to varied clinical outcomes, acutely like in sepsis, and over time in autoimmunity.

Integrity signals

Registry

Crossref · 10.1016/j.cyto.2019.154938

Cites

53 of 53 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Both individuals with DS and mouse models of DS experience constitutive hyperactivation of interferon (IFN) signaling with signs of chronic inflammation and immune dysregulation, which could exacerbate the neuroinflammatory response.

    “Notably, both individuals with DS and mouse models of DS experience constitutive hyperactivation of interferon (IFN) signaling with signs of chronic inflammation and immune dysregulation,30,31,32,33,34,35,36,37,38,39,40 that could exacerbate the neuroinflammatory response.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [33]

  • People with DS present increased IFN signaling likely driven by triplication of four of the six IFN receptors encoded on HSA21, rather than by massive elevation of IFN ligands, and this has been associated with chronic immune dysregulation.

    “people with DS present an increased IFN signaling likely driven by triplication of four of the six IFN receptors encoded on HSA21,36 rather than by massive elevation of the IFN ligands themselves as seen in interferonopathies,80 and this has been associated with chronic immune dysregulation.”

    From Interferon signaling modulates Down syndrome-associated Alzheimer’s disease pathology in a mouse model (2025) · cites this paper as [33]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Huggard, D., Kelly, L., Ryan, E., McGrane, F., Lagan, N., Roche, E., Balfe, J., Leahy, T. R., Franklin, O., Doherty, D. G., & Molloy, E. J.
Affiliations
Trinity College Dublin (IE)
Corresponding author
Huggard, Dean
ORCID
Venue
Cytokine
Publisher
Elsevier BV
Published
2020-03
Volume
127
Pages
154938
ISSN
1043-4666 (ISSN-L)
DOI
10.1016/j.cyto.2019.154938
OpenAlex
W2991488674
Cited by
94
References
53
Citations by year
2026: 14 · 2025: 16 · 2024: 15 · 2023: 16 · 2022: 11 · 2021: 15 · 2020: 7
FWCI
7.60
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Cytokine (publishedVersion)
  • PubMed (publishedVersion)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders
National Children's Research Centre
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
Down syndrome, systemic inflammation, cytokines, congenital heart disease, IL-10, interleukin-1 receptor antagonist, erythropoietin, vascular endothelial growth factor, GM-CSF, sepsis, autoimmunity, children
MeSH terms
Child, Child, Preschool, Down Syndrome, Enzyme-Linked Immunosorbent Assay, Female, Heart Defects, Congenital, Humans, Infant, Inflammation, Male, Cohort Studies, Biomarkers, Cytokines, Inflammation Mediators

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review