Elevation of proinflammatory cytokines in patients with Aicardi-Goutières syndrome
Open accessAbstract
OBJECTIVE: This study explores a large panel of cytokines in plasma and CSF of patients with Aicardi-Goutières syndrome (AGS) at different ages, in order to establish signatures of cytokines most predictive of AGS. METHODS: Plasma from 22 subjects with known mutations were assayed for cytokines using the Milliplex MAP Immunobead system, and compared to results from 8 age-matched normal controls. CSF of 11 additional patients with mutation-proven AGS was tested in an identical manner and compared to results from age-matched controls. Samples were banked and analysis was carried out retrospectively. RESULTS: Significant elevations were seen in FMS-related tyrosine kinase 3 ligand, IP-10, interleukin (IL)-12p40, IL-15, tumor necrosis factor α, and soluble IL 2 receptor α in both AGS patient plasma and CSF relative to controls. Additionally, this cytokine signature was able to correctly cluster 9 of 11 AGS cases based on CSF values. While most cytokines decreased exponentially with age, a subgroup including IP-10 demonstrated persistent elevation beyond early childhood. CONCLUSION: Patients with AGS exhibit plasma and CSF elevations of proinflammatory cytokines. Selected cytokines remain persistently elevated beyond the initial disease phase. This panel of proinflammatory cytokines may be considered for use as diagnostic and therapeutic markers of disease, and may permit improved understanding of disease pathogenesis.
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Many of the changes in the circulating proteome in people with Down syndrome are highly reminiscent of those observed in type I interferonopathies and other autoinflammatory conditions.
“Our study of the circulating proteome in people with DS, the largest and most comprehensive study of this kind reported to date, reveals that T21 causes profound immune dysregulation, with many of the changes being highly reminiscent of those observed in type I interferonopathies and other autoinflammatory conditions54,58–60,88 (Table 1).”
From Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation (2017) · cites this paper as [60]
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- Authors
- Takanohashi, A., Prust, M., Wang, J., Gordish-Dressman, H., Bloom, M., Rice, G. I., Schmidt, J. L., Crow, Y. J., Lebon, P., Kuijpers, T. W., Nagaraju, K., & Vanderver, A.
- Affiliations
- Children's National (US)
- From the Center for Genetic Medicine Research (A.T., H.G.-D., J.L.S., K.N., A.V.), Department of Neurology (M.P., J.L.S., A.V.), Biostatistics and Informatics Unit, Center for Clinic and Community Research (J.W.), and Hospitalist Medicine Division (M.B.), Children's National Medical Center, Washington, DC; Genetic Medicine (G.I.R., Y.J.C.), University of Manchester, Manchester Academic Heath Science Centre, Central Manchester University Hospitals, Manchester, UK; Hopital Cochin-Saint Vincent de Paul...
- ORCID
- Venue
- Neurology
- Published
- 2013-03-12
- Volume
- 80
- Issue
- 11
- Pages
- 997-1002
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3653200
- OpenAlex
- W2067625861
- Cited by
- 25
- References
- 19
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 2 · 2022: 4 · 2020: 1 · 2018: 1 · 2017: 5 · 2016: 1 · 2015: 3 · 2014: 1
- FWCI
- 0.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- U.S. Department of Defense (W81XWH1110809, W81XWH-11-1-, W81XWH, W81XWH1110782, W81XWH0510616)
- American Academy of Neurology
- European Commission (241779, 2007–2013, FP7 2007-2013, FP7/2007)
- Association Européenne contre les Leucodystrophies
- National Institutes of Health (FP7/2007-2013, W81XWH, K26OD011171)
- National Institute of Neurological Disorders and Stroke (K08NS060695)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR050478)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD053177, R24HD050846)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Keywords
- Aicardi-Goutières syndrome, inflammatory cytokines, cerebrospinal fluid, plasma cytokines, CXCL10, IL-12p40, IL-15, TNF-α, soluble IL-2 receptor alpha, cytokine signature, diagnostic biomarkers, pathogenesis
- MeSH terms
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Nervous System Malformations, Retrospective Studies, Biomarkers, Cytokines, Inflammation Mediators, Autoimmune Diseases of the Nervous System
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