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Predictive Value of Antibodies to Cyclic Citrullinated Peptide in Patients with Very Early Inflammatory Arthritis
KARIM RAZA, MIKE BREESE, PETER NIGHTINGALE, KANTA KUMAR, TANYA POTTER, DAVID M. CARRUTHERS, DEVA SITUNAYAKE, CAROLINE GORDON, CHRISTOPHER D. BUCKLEY, MIKE SALMON, and GEORGE D. KITAS
ABSTRACT. Methods. A cross-sectional study was performed in patients with established inflammatory and noninflammatory disease to validate the assay in our unit and confirm previously reported sensitivities and specificities of anti-CCP antibodies. Subsequently, patients with synovitis of ≤ 3 months' duration were followed for 72 weeks and the ability of anti-CCP antibodies and RF to predict the development of rheumatoid arthritis (RA) and persistent inflammatory arthritis was assessed. Results. One hundred twenty-four patients were assessed in the initial cross-sectional study. Anti-CCP antibodies and RF were detected by ELISA in only 4% of patients with non-RA inflammatory disease and in no patient with noninflammatory disease. Ninety-six patients with very early synovitis were assessed longitudinally. In these patients with early arthritis, the combination of anti-CCP antibodies and RF had a specificity, positive predictive value (PPV), sensitivity, and negative predictive value (NPV) for a diagnosis of RA of 100%, 100%, 58%, and 88%, respectively. The specificity, PPV, sensitivity, and NPV of this antibody combination for the development of persistent disease-fulfilling classification criteria for RA were 97%, 86%, 63%, and 91%, respectively. Conclusion. In patients with synovitis of ≤ 3 months' duration, a combination of anti-CCP antibodies and RF has a high specificity and PPV for the development of persistent RA. This autoantibody combination can be used to identify patients with disease destined to develop RA who may be appropriate for very early intervention. (J Rheumatol 2005;32:231-8) Key Indexing Terms:
CYCLIC CITRULLINATED PEPTIDE
From the MRC Centre for Immune Regulation, Division of Immunity and Infection, The University of Birmingham, Birmingham; Department of Rheumatology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham; Regional Department of Clinical Immunology and Department of Rheumatology, Dudley Group of Hospitals NHS Trust, Dudley; and Wolfson Computer Laboratory, Queen Elizabeth Medical Centre, Birmingham, UK. Supported by the Arthritis Research Campaign (ARC) and the Dudley Group of Hospitals NHS Trust R&D Directorate. K. Raza, PhD, MRCP, Clinical Senior Lecturer; K. Kumar, Research Nurse; C. Gordon, MD, FRCP, Reader in Rheumatology; C.D. Buckley, PhD, MRCP, Professor of Clinical Rheumatology, MRC Centre for Immune Regulation, Department of Rheumatology, City Hospital, Birmingham; M. Breese, BSc, FIMLS, Chief Biomedical Scientist Immunology, Regional Department of Clinical Immunology, Dudley Group of Hospitals NHS Trust; P. Nightingale, PhD, Statistician, Wolfson Computer Laboratory, Queen Elizabeth Medical Centre; T. Potter, MRCP, Specialist Registrar in Rheumatology; G.D. Kitas, PhD, FRCP, Consultant Rheumatologist, Department of Rheumatology, Dudley Group of Hospitals NHS Trust; D.M. Carruthers, PhD, MRCP, Consultant Rheumatologist; R.D. Situnayake, MD, FRCP, Consultant Rheumatologist, Department of Rheumatology, City Hospital, Birmingham; M. Salmon, PhD, Professor of Experimental Rheumatology, MRC Centre for Immune Regulation. Address reprint requests to Dr. K. Raza, MRC Centre for Immune Regulation, Division of Immunity and Infection, The University of Birmingham, Birmingham, B15 2TT, UK. E-mail: k.raza@bham.ac.uk Submitted March 30, 2004; revision accepted September 22, 2004. |