ArticleAnnals of the rheumatic diseases2016
Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification.
Article in Annals of the rheumatic diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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Who cites it
157 citing papers in PubMed, 248 citations in OpenAlex.
- A Randomized, Placebo-Controlled Trial of Hydroxychloroquine in Incomplete Lupus.Arthritis & rheumatology (Hoboken, N.J.) · 2026Trial
- Suppression of Serum Interferon-γ Levels as a Potential Measure of Response to Ustekinumab Treatment in Patients With Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2021Trial
- InterferonFrontiers in immunology · 2020Trial
- A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.Human molecular genetics · 2018Trial
- Autophagy determines the fate of immune cells by regulating metabolic remodeling and PANoptosis (Review).International journal of molecular medicine · 2026Review
- Serum IgA autoantibody profiling in systemic lupus erythematosus reveals associations with disease phenotypes.RMD open · 2026Article
- The role of HIF-1α in innate immune mechanisms and autoimmunity: A double-edged sword.The Journal of biological chemistry · 2026Review
- Type I interferon-dependent and -independent signaling underlie autoantibody production in a murine lupus model.Journal of translational autoimmunity · 2026Article
- A symposium update on the key perspectives in systemic sclerosis and systemic lupus erythematosus.Journal of translational autoimmunity · 2026Review
- Interferon-induced protein 44-like promoter Hypomethylation as an epigenetic hallmark of systemic lupus erythematosus.Journal of translational medicine · 2026Article
- Germinal-centre and extrafollicular B cell pathways in systemic lupus erythematosus.Nature reviews. Rheumatology · 2026Review
- PPAR-α Agonist Suppresses Expression of Immune Mediators in B Cells in a Murine Model of Systemic Lupus Erythematosus.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Recent developments in the use of biomarkers as diagnostic tools in patients with systemic lupus erythematosus: a narrative review.EULAR rheumatology open · 2026Review
- IFNγ-induced IRF1 synergizes with TLR7 signals to tune the IRF4-IRF8 axis and drive pathogenic effector B cell fate.bioRxiv : the preprint server for biology · 2026Article
- Immune profiling of anti-SSA-positive at-risk individuals reveals increased type I IFN activity preceding lymphocyte abnormalities in Sjögren's disease.Frontiers in immunology · 2026Article
- Transposable elements as a possible missing link between genetic predisposition and environmental triggers of autoimmune disorders: insights from type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.Frontiers in immunology · 2026Review
- Ultrasensitive quantification of serum IFN-α and IFN-γ in systemic lupus erythematosus: A cross-sectional observational study.PLoS medicine · 2025Observational
- Dysregulated soluble immune mediators and lupus-associated autoantibody specificities inform the development of immune indexes that characterise classified SLE transition and SLE disease activity.Lupus science & medicine · 2025Article
- The Type I Interferon Axis in Systemic Autoimmune Diseases: From Molecular Pathways to Targeted Therapy.Biomolecules · 2025Review
- Article
97 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
objectivesThe relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE.
methodsSerial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.3 years) and unaffected healthy controls matched by age (±5 years), gender, race and time of sample procurement were obtained from the Department of Defense Serum Repository. Levels of serum IFN-α activity, IFN-associated mediators and autoantibodies were evaluated and temporal relationships assessed by growth curve modelling, path analysis, analysis of covariance and random forest models.
resultsIn cases, but not matched controls, autoantibody specificities and IFN-associated mediators accumulated over a period of years, plateauing near the time of disease classification (p<0.001). Autoantibody positivity coincided with or followed type II IFN dysregulation, preceding IFN-α activity in growth curve models, with elevated IFN-α activity and B-lymphocyte stimulator levels occurring shortly before SLE classification (p≤0.005). Cases were distinguished by multivariate random forest models incorporating IFN-γ, macrophage chemoattractant protein (MCP)-3, anti-chromatin and anti-spliceosome antibodies (accuracy 93% >4 years pre-classification; 97% within 2 years of SLE classification).
conclusionsYears before SLE classification, enhancement of the type II IFN pathway allows for accumulation of autoantibodies and subsequent elevations in IFN-α activity immediately preceding SLE classification. Perturbations in select immunological processes may help identify at-risk individuals for further clinical evaluation or participation in prospective intervention trials.
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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.