Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Anti-Nucleosome Antibodies Correlate with Temporal Fluctuations in Disease Activity in Systemic Lupus Erythematosus.
Timothy1, Li, Morrison2, Stacey, Lou3, Wendy, Reich2, Heather, Aghdassi4, Ellie, Gladman5, D. D., Urowitz1, Murray B.
Toronto Western Hospital and University of Toronto, Toronto, ON
The Toronto Western Hospital, Toronto, ON
University of Toronto, Toronto, ON
University Health Network, Toronto, ON
The Arthritis Program, Toronto Western Hospital and Division of Rheumatology, Toronto Western Hospital and University of Toronto, Toronto, ON
Toronto Western Research Institute, University Health Network, Toronto, ON
The clinical course of SLE is characterized by unpredictable disease exacerbations. Current biomarkers (anti-dsDNA antibodies and complement (C3)) function poorly in forecasting these events. This limits their utility as reliable markers of disease activity, generating interest in the identification of novel biomarkers. Anti-nucleosome antibodies are increased in SLE patients and are associated with disease activity. The aim of this study was to examine the utility of anti-nucleosome antibodies as a flare-specific biomarker in SLE.
51 SLE patients satisfying >= 4 ACR criteria and 49 healthy controls were recruited. Patients were followed over a 14-month period with at least 3 clinical and biochemical assessments over that time. Clinical data and blood samples were collected at the time of recruitment and at subsequent assessments to determine the SLEDAI-2K (S-2K). A modified S-2K (mS-2K) was calculated by subtracting the contribution of anti-dsDNA antibodies and complement from the global score. An ELISA was utilized to determine IgG anti-nucleosome antibody levels in patients and control with a threshold for anti-nucleosome positivity defined as values 3 SD above the mean for controls. Spearman's (non-parametric) rank correlation analysis was used to determine the correlation coefficient between variables. Logistic regression analysis was performed with outcome parameters defined as activity (mS-2K > 0) or no activity (mS-2K = 0). Analysis of longitudinally correlated data was assessed by mixed effects models. p values of less than 0.05 were considered statistically significant.
Anti-nucleosome antibodies were significantly elevated in SLE patients versus controls (p < 0.0001). Anti-nucleosome antibody levels show a statistically significant positive correlation with anti-dsDNA antibodies (r = 0.72, p < 0.0001) and a negative correlation with C3 levels (r =-0.42, p = 0.002). A moderate positive correlation (r = 0.32, p = 0.02) was found between anti-nucleosome antibodies and disease activity. The ability of anti-nucleosome antibodies to discriminate between patients with active (mS-2K > 0) and inactive disease was determined using an ROC curve analysis. Examination of the area under the curve (AUC) for C3 (0.63), anti-dsDNA (0.69) and anti-nucleosome (0.61) antibodies demonstrated that all 3 biomarkers functioned in a comparable fashion. To determine the utility of these 3 parameters to mirror changes in disease activity a mixed effects regression analysis was performed. Models combining C3 and anti-nucleosome antibodies (AIC = 1188.6) outperformed models with C3 and anti-dsDNA antibodies (AIC = 1191.4). In a model (AIC = 1185.8) incorporating all 3 parameters only anti-nucleosome antibodies (p < 0.0001) remained statistically significant.
Anti-nucleosome antibodies outperform traditional biomarkers in tracking with changes in SLE disease activity supporting the incorporation of this serological marker in the monitoring of SLE. The current shift towards multiplex platforms for autoantibody determination will facilitate the inclusion of this parameter into clinical practice.
To cite this abstract, please use the following information:
Timothy, Li, Morrison, Stacey, Lou, Wendy, Reich, Heather, Aghdassi, Ellie, Gladman, D. D., et al; Anti-Nucleosome Antibodies Correlate with Temporal Fluctuations in Disease Activity in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2269