Anti-dsDNA and Antichromatin Antibody Isotypes in Serologically Active Clinically Quiescent Systemic Lupus Erythematosus.
OBJECTIVE
Serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE) are clinically quiescent despite serologic activity. Since studies suggest that antichromatin antibodies are more sensitive than anti-dsDNA antibodies in detecting active SLE, and that immunoglobulin (Ig) G, in particular complement-fixing subclasses, may be more pathogenic than IgM, we investigated the levels of anti-dsDNA and antichromatin isotypes in SACQ patients as compared to non-SACQ patients with SLE.


METHODS
Levels of IgM, IgA, IgG, and IgG1-4 antichromatin and anti-dsDNA were measured by ELISA. SACQ was defined as ≥ 2 years with the SLE Disease Activity Index 2000 (SLEDAI-2K) at 2 or 4 from serologic activity, during which patients could be taking antimalarials, but not corticosteroids or immunosuppressives. Unselected non-SACQ patients with SLE were used as comparators. SACQ patient serum samples were further stratified based on subsequent development of flare, defined as clinical SLEDAI-2K ≥ 1 and/or treatment initiation. Nonparametric statistics were used, and generalized estimating equations were applied to account for multiple samples in the same patient.


RESULTS
SACQ patients' complement-fixing antichromatin and anti-dsDNA IgG subclasses were significantly higher than those of non-SACQ patients. When the sample drawn latest in a SACQ period was analyzed, there was no difference between antichromatin or anti-dsDNA isotype or IgG subclass levels between patients who flared and those who remained SACQ, nor were consistent trends seen when samples were examined during SACQ and flare in the same patient.


CONCLUSIONS
The SACQ phenotype does not arise from a lack of pathogenic anti-dsDNA and/or antichromatin autoantibodies. Neither increases in antichromatin nor anti-dsDNA isotype or IgG subclass levels were predictive of or coincident with flare in SACQ patients.
From the University of Toronto; Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital; Toronto Western Hospital; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, FRCPC, Rheumatology Fellow, University of Toronto, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; M.B. Urowitz, MD, FRCPC, Professor of Medicine, University of Toronto, and Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; D. Ibañez, MSc, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; T.T. Li, MSc, Medical Student, Arthritis Centre of Excellence, Division of Genetics and Development, Western Hospital Research Institute, University Health Network; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; J. Wither, MD, PhD, FRCPC, Professor of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network.
Amanda J
AJ
Steiman
From the University of Toronto; Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital; Toronto Western Hospital; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, FRCPC, Rheumatology Fellow, University of Toronto, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; M.B. Urowitz, MD, FRCPC, Professor of Medicine, University of Toronto, and Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; D. Ibañez, MSc, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; T.T. Li, MSc, Medical Student, Arthritis Centre of Excellence, Division of Genetics and Development, Western Hospital Research Institute, University Health Network; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; J. Wither, MD, PhD, FRCPC, Professor of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network.
Murray B
MB
Urowitz
From the University of Toronto; Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital; Toronto Western Hospital; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, FRCPC, Rheumatology Fellow, University of Toronto, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; M.B. Urowitz, MD, FRCPC, Professor of Medicine, University of Toronto, and Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; D. Ibañez, MSc, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; T.T. Li, MSc, Medical Student, Arthritis Centre of Excellence, Division of Genetics and Development, Western Hospital Research Institute, University Health Network; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; J. Wither, MD, PhD, FRCPC, Professor of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network.
Dominique
D
Ibañez
From the University of Toronto; Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital; Toronto Western Hospital; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, FRCPC, Rheumatology Fellow, University of Toronto, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; M.B. Urowitz, MD, FRCPC, Professor of Medicine, University of Toronto, and Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; D. Ibañez, MSc, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; T.T. Li, MSc, Medical Student, Arthritis Centre of Excellence, Division of Genetics and Development, Western Hospital Research Institute, University Health Network; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; J. Wither, MD, PhD, FRCPC, Professor of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network.
Timothy T
TT
Li
From the University of Toronto; Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital; Toronto Western Hospital; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, FRCPC, Rheumatology Fellow, University of Toronto, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; M.B. Urowitz, MD, FRCPC, Professor of Medicine, University of Toronto, and Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; D. Ibañez, MSc, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; T.T. Li, MSc, Medical Student, Arthritis Centre of Excellence, Division of Genetics and Development, Western Hospital Research Institute, University Health Network; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; J. Wither, MD, PhD, FRCPC, Professor of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network.
Dafna D
DD
Gladman
From the University of Toronto; Centre for Prognosis Studies in The Rheumatic Diseases, Toronto Western Hospital; Toronto Western Hospital; Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.A.J. Steiman, MD, FRCPC, Rheumatology Fellow, University of Toronto, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; M.B. Urowitz, MD, FRCPC, Professor of Medicine, University of Toronto, and Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; D. Ibañez, MSc, Biostatistician, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; T.T. Li, MSc, Medical Student, Arthritis Centre of Excellence, Division of Genetics and Development, Western Hospital Research Institute, University Health Network; D.D. Gladman, MD, FRCPC, Professor of Medicine, University of Toronto, and Deputy Director, Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital; J. Wither, MD, PhD, FRCPC, Professor of Medicine, University of Toronto, Arthritis Centre of Excellence, Division of Genetics and Development, Toronto Western Hospital Research Institute, University Health Network. jwither@uhnresearch.ca.
Joan
J
Wither
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D002843:Chromatin / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D001323:Autoantibodies; D002843:Chromatin; D007132:Immunoglobulin Isotypes; D004247:DNA
ANTI-DNA ANTIBODIES; ANTICHROMATIN ANTIBODIES; DISEASE ACTIVITY; OUTCOME; SEROLOGIC ACTIVITY; SYSTEMIC LUPUS ERYTHEMATOSUS