Anti-nucleosome antibodies outperform traditional biomarkers as longitudinal indicators of disease activity in systemic lupus erythematosus

Timothy Li; Stephenie D Prokopec; Stacey Morrison; Wendy Lou; Heather Reich; Dafna Gladman; Murray Urowitz; James Scholey; Paul R Fortin; Paul C Boutros; Joan Wither; Carolina Landolt-Marticorena

doi:10.1093/rheumatology/keu326

Anti-nucleosome antibodies outperform traditional biomarkers as longitudinal indicators of disease activity in systemic lupus erythematosus

Rheumatology (Oxford). 2015 Mar;54(3):449-57. doi: 10.1093/rheumatology/keu326. Epub 2014 Sep 5.

Affiliations

¹ 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.
² 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
³ 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.

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.

Conclusion: 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.

Keywords: anti-nucleosome antibodies; biomarkers; disease activity; systemic lupus erythematosus.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Antibodies, Anti-Idiotypic / blood*
Biomarkers / blood
Complement C3 / metabolism
Cross-Sectional Studies
DNA / immunology
Female
Humans
Longitudinal Studies
Lupus Erythematosus, Systemic / blood*
Lupus Erythematosus, Systemic / diagnosis*
Male
Middle Aged
Nucleosomes / immunology*
Prospective Studies
Sensitivity and Specificity
Severity of Illness Index*
Time Factors
Young Adult

Substances

Antibodies, Anti-Idiotypic
Biomarkers
Complement C3
Nucleosomes
DNA

Grants and funding

QNT 78341/Canadian Institutes of Health Research/Canada