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Cited by 144Down syndrome and intellectual disability researchImmunodeficiency and Autoimmune DisordersImmune Response and Inflammation

Immune Dysregulation in Children With Down Syndrome

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Huggard, Dean, Doherty, Derek G., Molloy, Eleanor J.·2020·Frontiers in Pediatrics
DOI 10.3389/fped.2020.00073PMC PMC7056667
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Abstract

Down syndrome (DS) is the most common genetic syndrome associated with immune defects. The extent of immune dysregulation in DS is substantial, spanning the innate and adaptive systems and including anomalies in: T and B cells, monocytes, neutrophil chemotaxis, circulating cytokines, and suboptimal antibody responses which all contribute to an increased risk of infections, poorer clinical outcomes and chronic inflammation in this vulnerable cohort. Other aspects of innate immunity may also be abnormal and contribute to the increased morbidity and warrant further interrogation such as: gamma delta T cell function, the inflammasome, Toll-like receptors and their pathways. Pharmacotherapies such as pavilizumab, pneumococcal and influenza immunizations, as well as potential immunoprophylactic agents such as pidotimod, azithromycin and Broncho-Vaxom may help alleviate the infectious consequences. Children with DS need to be managed with a heightened sense of awareness and urgency in the setting of sepsis and signs of chronic inflammation need regular screening and appropriate follow up.

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  • 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 [32]

    The Cytokines section (page unavailable) reports elevated IFN-γ and baseline inflammatory markers in people with Down syndrome; the Complement Pathway section links Down syndrome to type 1 interferonopathies and persistent inflammation. These passages support the human inflammation and immune-dysregulation portions, but do not establish constitutive hyperactivation of IFN signaling in both people and mouse models of Down syndrome. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • 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 [32]

    The Complement Pathway section associates Down syndrome with type 1 interferonopathies and persistent inflammation, broadly supporting the interferon-response and immune-dysregulation portions of the claim. Our copy does not state that increased signaling is driven by triplication of four of six interferon receptors on chromosome 21. The ligand comparison is attached to a different citation in the citing sentence. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Huggard, D., Doherty, D. G., & Molloy, E. J.
Affiliations
Trinity College Dublin (IE)
Corresponding author
Huggard, Dean
ORCID
Venue
Frontiers in Pediatrics
Publisher
Frontiers Media SA
Published
2020-02-27
Volume
8
Pages
73-73
ISSN
2296-2360 (ISSN-L)
DOI
10.3389/fped.2020.00073
PMC
PMC7056667
OpenAlex
W3007248785
Cited by
144
References
5
Citations by year
2026: 33 · 2025: 21 · 2024: 24 · 2023: 19 · 2022: 23 · 2021: 20 · 2020: 4
FWCI
2.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Pediatrics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion, cc-by-nc-sa)
  • Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
  • 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, immune dysregulation, primary immunodeficiency, T cell dysfunction, B cell dysfunction, monocytes, neutrophil chemotaxis, cytokines, antibody response, infection risk, chronic inflammation, γδ T cells, inflammasome, Toll-like receptors, pneumococcal vaccination, influenza vaccination, pidotimod, azithromycin, Broncho-Vaxom, sepsis, children

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