 |
|
|
 |
Serum Autoantibodies that Bind Citrullinated Fibrinogen Are Frequently Found in Patients with Rheumatoid Arthritis
JONATHAN A. HILL, JAMAL AL-BISHRI, DAFNA D. GLADMAN, EWA CAIRNS, and DAVID A. BELL ABSTRACT. Objective. Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases. Methods. In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis. Results. Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2. Conclusion. These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis. (First Release Aug 15 2006; J Rheumatol 2006;33:2115-9) Key Indexing Terms:
RHEUMATOID ARTHRITIS From the Department of Medicine, Division of Rheumatology, and Department of Microbiology and Immunology, University of Western Ontario, London, Ontario; Division of Rheumatology, London Health Sciences Centre, London, Ontario; the University of Toronto Rheumatic Disease Unit, and the Centre for Prognosis Studies in the Rheumatic Diseases, University Health Network, Toronto Western Hospital, Toronto, Ontario, Canada. Dr. Cairns and Dr. Bell contributed equally to this report. Supported by The Arthritis Society and the Internal Research Funds of the Department of Medicine, University of Western Ontario and London Health Sciences Centre. J.A. Hill is supported by a Canadian Institute of Health Research/K.M. Hunter Doctoral Research Award and E. Cairns is supported by an award from the Calder Foundation. J.A. Hill, BSc, Graduate Student, Department of Microbiology and Immunology, University of Western Ontario; J. Al-Bishri, MD, Rheumatology Fellow, Division of Rheumatology, London Health Sciences Centre; D.D. Gladman, MD, Professor, Department of Medicine, University of Toronto; E. Cairns, PhD, Associate Professor; D.A. Bell, MD, Professor, Department of Medicine and Microbiology and Immunology, University of Western Ontario. Address reprint requests to Dr. D.A. Bell, Rheumatology Centre, Monsignor Roney Building, St. Joseph's Health Centre, 268 Grosvenor Street, London, Ontario N6A 4V2. E-mail: david.bell@sjhc.london.on.ca Accepted for publication May 19, 2006.
|
