title: Anti-nucleosome antibodies outperform traditional biomarkers as longitudinal indicators of disease activity in systemic lupus erythematosus.
abstract: OBJECTIVE
  The aim of this study was to determine whether anti-nucleosome antibodies function as activity-specific biomarkers in SLE.
  
  
  METHODS
  Fifty-one patients were recruited and followed prospectively with periodic clinical and biochemical assessments over a 14-month period. Disease activity was determined by the SLEDAI-2K. Anti-nucleosome antibody levels were measured by an ELISA and its utility as an activity-specific biomarker as compared with that of anti-dsDNA antibodies and C3 was assessed both at baseline and in longitudinal analysis.
  
  
  RESULTS
  Anti-nucleosome antibodies were significantly elevated in SLE patients vs controls and showed a moderate positive correlation with disease activity. The utility of anti-nucleosome antibodies in identifying patients with active disease in a cross-sectional analysis was comparable to that of anti-dsDNA antibodies and C3. Analysis of variance demonstrated that the level of anti-nucleosome antibodies and C3 varied significantly with changes in disease activity over time. Changes in clinical state were not mirrored by changes in anti-dsDNA antibodies. In time-dependent analysis, anti-nucleosome antibodies showed a better fit over time than anti-dsDNA antibodies and C3. In pairwise comparisons, C3 and anti-nucleosome antibodies outperformed other models, including the conventional pairing of C3 and anti-dsDNA antibodies, however, no biomarker alone or as a group accurately predicted impending remissions or exacerbations.
  
  
  CONCLUSIONS
  Anti-nucleosome antibodies demonstrate greater fidelity as a biomarker for changes in SLE disease activity than traditional biomarkers, supporting the routine monitoring of this antibody in clinical practice.
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Timothy
authors.initials: T
authors.lastname: Li
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Stephenie D
authors.initials: SD
authors.lastname: Prokopec
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Stacey
authors.initials: S
authors.lastname: Morrison
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Wendy
authors.initials: W
authors.lastname: Lou
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Heather
authors.initials: H
authors.lastname: Reich
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University 
authors.forename: Dafna
authors.initials: D
authors.lastname: Gladman
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University 
authors.forename: Murray
authors.initials: M
authors.lastname: Urowitz
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Scholey
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Fortin
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University 
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University 
authors.forename: Joan
authors.initials: J
authors.lastname: Wither
authors.affiliation: Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network (UHN), Ontario Institute for Cancer Research, University of Toronto Lupus Clinic, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital, University Health Network, Division of Biostatistics, Dalla Lana School of Public Health, Department of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, ON, Centre de recherche du CHU de Québec, CHU de Québec, Division of Rheumatology, Department of Medicine, CHU de Québec and Faculty of Medicine, Université Laval, Quebec City, QC, Department of Immunology, Department of Medical Biophysics and Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada. Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University 
authors.forename: Carolina
authors.initials: C
authors.lastname: Landolt-Marticorena
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003176:Complement C3 / Q000378:metabolism; D003430:Cross-Sectional Studies; D004247:DNA / Q000276:immunology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D009707:Nucleosomes / Q000276:immunology*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D015415:Biomarkers; D003176:Complement C3; D009707:Nucleosomes; D004247:DNA
keywords: anti-nucleosome antibodies; biomarkers; disease activity; systemic lupus erythematosus