Autoantibody‐Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity
| العنوان: | Autoantibody‐Positive Healthy Individuals Display Unique Immune Profiles That May Regulate Autoimmunity |
|---|---|
| المؤلفون: | Paul J. Utz, Samantha Slight-Webb, C G Fathman, Judith A. James, Joel M. Guthridge, Lauren L. Ritterhouse, Joan T. Merrill, Holden T. Maecker, Melissa E. Munroe, Rufei Lu |
| المصدر: | Arthritis & Rheumatology (Hoboken, N.j.) |
| بيانات النشر: | John Wiley and Sons Inc., 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Anti-nuclear antibody, Autoimmunity, medicine.disease_cause, Monocytes, immune system diseases, Granulocyte Colony-Stimulating Factor, Leukocytes, Immunology and Allergy, Lupus Erythematosus, Systemic, skin and connective tissue diseases, Aged, 80 and over, Stem Cell Factor, Systemic lupus erythematosus, Interleukin-12 Subunit p40, Interleukin-17, Nuclear Proteins, Middle Aged, Flow Cytometry, Healthy Volunteers, 3. Good health, STAT1 Transcription Factor, DNA Topoisomerases, Type I, Ribonucleoproteins, Antibodies, Antinuclear, Cytokines, Female, Interleukin 17, Adult, Ribosomal Proteins, STAT3 Transcription Factor, medicine.medical_specialty, Plasma Cells, Immunology, B-Lymphocyte Subsets, Systemic Lupus Erythematosus, Article, Immunophenotyping, Autoimmune Diseases, Interferon-gamma, Young Adult, 03 medical and health sciences, Sex Factors, Rheumatology, Internal medicine, medicine, Humans, B-cell activating factor, Aged, Autoantibodies, Autoimmune disease, Lupus erythematosus, Tumor Necrosis Factor-alpha, business.industry, Autoantibody, Interferon-alpha, Interferon-beta, Phosphoproteins, medicine.disease, Interleukin 1 Receptor Antagonist Protein, stomatognathic diseases, Logistic Models, 030104 developmental biology, Endocrinology, Case-Control Studies, Multivariate Analysis, business, Centromere Protein B |
| الوصف: | Objective Antinuclear 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. Methods Healthy individuals (n = 790) were screened for autoantibodies specific for 11 antigens associated with lupus, systemic sclerosis, and Sjogren'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. Results Of 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). Conclusion ANA-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. |
| اللغة: | English |
| تدمد: | 2326-5205 2326-5191 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da8fa521ad71a9191ce7715ec20481f3Test http://europepmc.org/articles/PMC5042816Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....da8fa521ad71a9191ce7715ec20481f3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23265205 23265191 |
|---|