Abstract
Down syndrome (DS) is a unique genetic disease caused by the presence of an extra copy of chromosome 21, which carries four of the six interferon receptor (IFN-R) genes on its long arm. Recent studies reporting higher levels of interferon-stimulated gene (ISG) expression in primary immune cells studied ex vivo have suggested that the additional copies of the IFN-R genes in DS result in mild interferonopathy. In this review, we analyze the potential clinical and immunological impacts of this interferonopathy in DS. We per-formed a literature review to explore the epidemiology and risks of celiac disease, type 1 diabetes, thyroid dysfunction, mucocutaneous manifestations, infectious diseases (including COVID-19), and Alzheimer’s disease in individuals with DS relative to the general population with or without iatrogenic exposure to interferons. We analyzed immunophenotyping data and the current experimental evidence concerning IFN-R expression, constitutive JAK-STAT activation, and ISG overexpression in DS. Despite the lack of direct evidence that implicating this mild interferonopathy directly in illnesses in individuals with DS, we high-light the challenges ahead and directions that could be taken to determine more clearly the biological impact of interferonopathy on various immune-related conditions in DS.
Original language | English (US) |
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Pages (from-to) | 5187-5200 |
Number of pages | 14 |
Journal | Journal of Inflammation Research |
Volume | 14 |
DOIs | |
State | Published - 2021 |
Externally published | Yes |
Keywords
- Celiac disease
- Down syndrome
- Gene dosage effect
- Interferon receptors
- JAK-STAT
- T cells
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology