ArticleThe Lancet. Neurology2013
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.
Article in The Lancet. Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 242 papers, 2 of them syntheses that pooled it.
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Who cites it
242 citing papers in PubMed, 2 syntheses or guidelines pooled it, 433 citations in OpenAlex.
- Oligoprotein type I interferon signatures, but not TREX1 variants, increase risk of systemic lupus erythematosus in UK Biobank.Nature communications · 2026Pooled it
- Detecting fitness epistasis in recently admixed populations with genome-wide data.BMC genomics · 2020Pooled it
- Reverse transcriptase inhibitors in Aicardi-Goutières syndrome: A crossover clinical trial.Developmental medicine and child neurology · 2025Trial
- Iterative genetic testing identifiesJournal of human immunity · 2026Article
- The therapeutic potential of transposable element activity modulation.EMBO molecular medicine · 2026Review
- Neonatal Aicardi-Goutières syndrome presenting with macrophage activation syndrome-like hyperinflammation and severe congenital glaucoma: a case report.Pediatric rheumatology online journal · 2026Article
- A molecular glue induces aberrant STING oligomerization and inhibits autoinflammatory diseases.Signal transduction and targeted therapy · 2026Article
- An interferonopathy associated with a monoallelic variant in TRIM28.Pediatric rheumatology online journal · 2026Article
- The Development of UM-232, a Covalent STING Antagonist.ACS medicinal chemistry letters · 2026Article
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- Genetic determinants of childhood onset systemic lupus erythematosus.Lupus science & medicine · 2026Article
- Autoinflammatory syndromes of STING and TREX1 dysfunction.The Journal of clinical investigation · 2026Review
- The STING HAQ haplotype and clinical non-penetrance in COPA syndrome.The Journal of experimental medicine · 2026Article
- A novel patient-Centered approach to clinical trial readiness in rare diseases: Application in Aicardi-Goutières Syndrome (AGS).Molecular genetics and metabolism · 2026Article
- [Interferon scores in the management of rheumatic systemic diseases].Zeitschrift fur Rheumatologie · 2026Review
- The Development of UM-203, A Reversible Covalent STING Antagonist.ACS medicinal chemistry letters · 2026Article
- Gut metabolites identified in cerebrospinal fluid of genetic interferonopathy support gut-brain endothelial dysfunction.Clinical & translational immunology · 2026Article
- cGAS inhibitor IMSB301 modifies interferon signalling in peripheral mononuclear cells ofClinical & translational immunology · 2026Article
- SAVI: molecular mechanisms, clinical spectrum and precision medicine approaches beyond type-I IFN.Frontiers in immunology · 2026Review
- Ultrasensitive Test Systems Are Required to Quantify Interferon Alpha Protein in Serum Samples.European journal of immunology · 2025Article
182 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors at 20 institutions in 14 countries.
Funding
Abstract
backgroundAicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials.
methodsIn this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2·466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins.
findings74 (90%) of 82 patients had a positive interferon score (median 12·90, IQR 6·14-20·41) compared with two (7%) of 29 controls (median 0·93, IQR 0·57-1·30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=-0·604; serum, r=-0·289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that measurable antiviral activity was related to interferon α production. We did not record significantly increased concentrations of autoantibodies to interferon subtypes in patients with AGS, or an association between the presence of autoantibodies and interferon score or serum interferon activity.
interpretationAGS is consistently associated with an interferon signature, which is apparently sustained over time and can thus be used to differentiate patients with AGS from controls. If future studies show that interferon status is a reactive biomarker, the measurement of an interferon score might prove useful in the assessment of treatment efficacy in clinical trials.
fundingEuropean Union's Seventh Framework Programme; European Research Council.
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