ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Autoantibody-Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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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
57 citing papers in PubMed, 99 citations in OpenAlex.
- Mapping Autoantibodies in Children With Acute Rheumatic Fever.Frontiers in immunology · 2021Trial
- Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.The Journal of allergy and clinical immunology · 2020Trial
- Serum biomarkers of inflammation and muscle strength among women with systemic lupus erythematosus.Cytokine · 2017Trial
- Clinical Conditions Associated With a High Antinuclear Antibody Titer in Individuals Without Autoimmune Disease.Arthritis care & research · 2026Article
- Deciphering the interferon gene signature spectrum: association with the clinical heterogeneity of Sjögren's disease.Frontiers in immunology · 2026Article
- Differences in IgG Sialylation Distinguish Asymptomatic From Symptomatic Antinuclear Antibody-Positive Individuals.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Cross-Population Analysis of Sjögren's Syndrome Polygenic Risk Scores and Disease Prevalence: A Pilot Study.Genes · 2025Article
- Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.Lupus science & medicine · 2025Article
- Crystalline silica exposure induces multiple systemic autoimmune phenotypes including inflammatory arthritis and nephritis in Collaborative Cross mice with differing sub-clinical autoimmune profiles.bioRxiv : the preprint server for biology · 2025Article
- Immunological Avalanches in Renal Immune Diseases.Biomedicines · 2025Review
- Article
- CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases.Annals of dermatology · 2024Article
- Screening for autoimmune diseases in apparently healthy antinuclear antibody positive individuals.Frontiers in medicine · 2024Article
- Ancestry-based differences in the immune phenotype are associated with lupus activity.JCI insight · 2023Article
- Clinical diagnoses associated with a positive antinuclear antibody test in patients with and without autoimmune disease.BMC rheumatology · 2023Article
- Editorial: Environmental factors in autoimmunity.Frontiers in immunology · 2023Article
- Serum 25(OH)D levels are associated with disease activity and renal involvement in initial-onset childhood systemic lupus erythematosus.Frontiers in pediatrics · 2023Article
- Occupational trichloroethylene exposure and antinuclear antibodies: a cross-sectional study in China.Occupational and environmental medicine · 2022Article
- Autoantibodies in COVID-19 correlate with antiviral humoral responses and distinct immune signatures.Allergy · 2022Article
- A New Method for the Assessment of Myalgia in Interstitial Lung Disease: Association with Positivity for Myositis-Specific and Myositis-Associated Antibodies.Diagnostics (Basel, Switzerland) · 2022Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveAntinuclear antibodies (ANAs) are detected in ∼18% of females, yet autoimmune disease develops in only 5-8%. Immunologic differences between ANA-positive healthy individuals and patients with systemic lupus erythematosus (SLE) may elucidate the regulatory mechanisms by which ANA-positive individuals avoid transition to clinical autoimmune disease.
methodsHealthy individuals (n = 790) were screened for autoantibodies specific for 11 antigens associated with lupus, systemic sclerosis, and Sjögren's syndrome. From this screening, 31 European American ANA-positive healthy individuals were selected and demographically matched to ANA-negative controls and SLE patients. Serum cytokine profiles, leukocyte subset frequency, and reactivity were analyzed by multiplex assays, immunophenotyping, and phosphospecific flow cytometry.
resultsOf 790 individuals screened, 57 (7%) were ANA-positive. The majority of proinflammatory cytokines, including interferon-γ (IFNγ), tumor necrosis factor, interleukin-17 (IL-17), and granulocyte colony-stimulating factor, exhibited a stepwise increase in serum levels from ANA-negative controls to ANA-positive healthy individuals to SLE patients (P < 0.0001). IFNα, IFNβ, IL-12p40, and stem cell factor/c-Kit ligand were increased in SLE patients only (P < 0.05). B lymphocyte stimulator (BlyS) was elevated in SLE patients but decreased in ANA-positive individuals (P < 0.001). Further, IL-1 receptor antagonist (IL-1Ra) was down-regulated in SLE patients only (P < 0.0001). ANA-positive individuals had increased frequencies of monocytes, memory B cells, and plasmablasts and increased levels of pSTAT-1 and pSTAT-3 following IFNα stimulation compared with ANA-negative controls (P < 0.05).
conclusionANA-positive healthy individuals exhibit dysregulation in multiple immune pathways yet differ from SLE patients by the absence of elevated IFNs, BLyS, IL-12p40, and stem cell factor/c-Kit ligand. Further, severely decreased levels of IL-1Ra in SLE patients compared with ANA-positive individuals may contribute to disease development. These results highlight the importance of IFN-related pathways and regulatory elements in SLE pathogenesis.
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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.