ArticleScience advances2023
Multidimensional definition of the interferonopathy of Down syndrome and its response to JAK inhibition.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Revisiting down syndrome through the lens of interferonopathy and innate immune dysregulation.Frontiers in immunology · 2026Pooled it
- Trial
- The Mediator complex: co-transcriptional regulation and beyond.RNA biology · 2026Review
- Fasudil induces anti-inflammatory transcriptomic changes and increased proliferation in human trisomy 21 neural progenitor cells.Biology open · 2026Article
- Clinical considerations for immune dysregulation and immunodeficiency in Down syndrome.Journal of human immunity · 2026Review
- Immune dysregulation in children with Down syndrome: clinical implications and emerging therapies.Current opinion in rheumatology · 2026Review
- Metabolomic Profiles in Down Syndrome: A Scoping Review of Convergent and Context-Dependent Patterns.Journal of intellectual disability research : JIDR · 2026Article
- Progressive deterioration of adaptive immune repertoires in Down syndrome linked to interferon hyperactivity and lymphoid tissue disorganization.bioRxiv : the preprint server for biology · 2026Article
- RegRegSEA: a web server for regulatory region set enrichment analysis of epigenomic data.Nucleic acids research · 2026Article
- How I Treat: Immune dysregulation in Down syndrome.Journal of human immunity · 2026Review
- Aberrant chromatin remodeling influences human neural cell fate change in Trisomy 21.bioRxiv : the preprint server for biology · 2026Article
- Article
- Transcriptomic and proteomic evidence for noncanonical hydrogen sulfide metabolism and immune dysregulation in Down Syndrome.Scientific reports · 2026Article
- Systematic multi-omic deconvolution of the clinical heterogeneity of Down syndrome.Nature communications · 2026Article
- Molecular and cellular processes disrupted in the early postnatal Down syndrome prefrontal cortex.Science (New York, N.Y.) · 2026Article
- Selective chr21 homolog silencing reveals polymorphisms influence the epigenetic silencing and functional dosage of RWDD2B.American journal of human genetics · 2026Article
- Precision medicine for Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Anti-inflammatory and pro-proliferative effects of fasudil in human trisomy 21 neural progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Article
- Searching for New Possible Peripheral Biomarkers of Cognitive Decline in Down Syndrome: The Role of IL-18 Pathway and its Interaction with TGF-β1 and TNF-α.Neuromolecular medicine · 2026Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Individuals with Down syndrome (DS) display chronic hyperactivation of interferon signaling. However, the clinical impacts of interferon hyperactivity in DS are ill-defined. Here, we describe a multiomics investigation of interferon signaling in hundreds of individuals with DS. Using interferon scores derived from the whole blood transcriptome, we defined the proteomic, immune, metabolic, and clinical features associated with interferon hyperactivity in DS. Interferon hyperactivity associates with a distinct proinflammatory phenotype and dysregulation of major growth signaling and morphogenic pathways. Individuals with the highest interferon activity display the strongest remodeling of the peripheral immune system, including increased cytotoxic T cells, B cell depletion, and monocyte activation. Interferon hyperactivity accompanies key metabolic changes, most prominently dysregulated tryptophan catabolism. High interferon signaling stratifies a subpopulation with elevated rates of congenital heart disease and autoimmunity. Last, a longitudinal case study demonstrated that JAK inhibition normalizes interferon signatures with therapeutic benefit in DS. Together, these results justify the testing of immune-modulatory therapies in DS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.