title: Lack of Interferon and Proinflammatory Cyto/chemokines in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.
abstract: OBJECTIVE
  Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) remain clinically quiescent for prolonged periods despite anti-dsDNA antibodies and/or low complements, indicating the presence of immune complexes. The immune mechanisms leading to this quiescence are unknown. However, in addition to activating complement, immune complex uptake by various cells leads to the production of interferon (IFN)-α and other proinflammatory factors that are also involved in tissue damage. Here we investigate whether production of these factors is reduced in SACQ patients.
  
  
  METHODS
  The levels of 5 IFN-induced genes and 19 cyto/chemokines were measured in SACQ patients and were compared with those in serologically and clinically active (SACA) and serologically and clinically quiescent (SQCQ) patients. SACQ and SQCQ were defined as ≥ 2 years without clinical activity, with/without persistent serologic activity, respectively, and off corticosteroids/immunosuppressives. SACA was defined as disease activity compelling immunosuppression. Levels of OAS1, IFIT1, MX1, LY6E, and ISG15 were measured by quantitative real-time polymerase chain reaction (PCR) and a composite score (IFN-5) derived from this. Plasma cyto/chemokines were measured by Luminex assay. Nonparametric univariate and logistic regression analyses were conducted.
  
  
  RESULTS
  There were no differences in gene expression or cyto/chemokine levels between SACQ and SQCQ patients. The SACQ IFN-5 score was significantly lower than that of SACA (p = 0.003) and was driven by SACQ status, not by autoantibody profile or disease duration. Levels of granulocyte-macrophage colony-stimulating factor, interleukin (IL) 6, IL-10, IFN-γ-inducible protein 10, monocyte chemoattractant protein 1, and tumor necrosis factor-α were significantly lower in SACQ than SACA.
  
  
  CONCLUSIONS
  The levels of proinflammatory factors in SACQ mirror those of SQCQ patients, indicating reduced production of these factors despite the presence of immune complexes.
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Steiman
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Dominique
authors.initials: D
authors.lastname: Ibañez
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Babak
authors.initials: B
authors.lastname: Noamani
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Carolina
authors.initials: C
authors.lastname: Landolt-Marticorena
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Murray B
authors.initials: MB
authors.lastname: Urowitz
authors.affiliation: From the University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; Division of Rheumatology, Department of Medicine, and Department of Immunology, University of Toronto; Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, MSc, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto; D.D. Gladman, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network; D. Ibañez, MSc, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network; B. Noamani, MSc, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network; C. Landolt-Marticorena, MD, PhD, FRCP, Division of Rheumatology, Department of Medicine, University of Toronto; M.B. Urowitz, MD, FRCP, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, and Division of Rheumatology, Department of Medicine, University of Toronto, and Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Wes
authors.forename: Joan E
authors.initials: JE
authors.lastname: Wither
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D018925:Chemokines / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007372:Interferons / Q000097:blood*; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008991:Monitoring, Physiologic; D015999:Multivariate Analysis; D010045:Outpatients / Q000706:statistics & numerical data; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012698:Serologic Tests; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D007372:Interferons
keywords: CHEMOKINE; CYTOKINE; INTERFERON; SYSTEMIC LUPUS ERYTHEMATOSUS