Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase

• Published in: Annals of the rheumatic diseases Vol. 70; no. 5; pp. 772 - 777
• Main Authors: van de Sande, M G H, de Hair, M J H, van der Leij, C, Klarenbeek, P L, Bos, W H, Smith, M D, Maas, M, de Vries, N, van Schaardenburg, D, Dijkmans, B A C, Gerlag, D M, Tak, P P
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and European League Against Rheumatism 01.05.2011; BMJ Publishing Group; Elsevier Limited
• Subjects: Adult; Antigens; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Arthroscopy; Autoantibodies - blood; Biological and medical sciences; Biomarkers - blood; Biopsy; Case-Control Studies; Disease Progression; Diseases of the osteoarticular system; Female; Follow-Up Studies; Health risk assessment; Humans; Hypotheses; Inflammation; Inflammatory joint diseases; Knee Joint - pathology; Magnetic Resonance Imaging - methods; Male; Medical sciences; Middle Aged; Peptides; Peptides, Cyclic - immunology; Proteins; Rheumatism; Rheumatoid arthritis; Rheumatoid Factor - blood; Rheumatology; Synovial Membrane - pathology; Synovitis - etiology; Synovitis - immunology; Synovitis - pathology; Young Adult; Immunopathology; Chronic; Synovial membrane; Rheumatoid arthritis; Diseases of the osteoarticular system; Rheumatology; Autoimmune disease; Inflammatory joint disease
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/ard.2010.139527

Background The aetiology of rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disorder, is poorly understood. It is currently unknown whether the disease process starts in the synovium, the primary target of RA, or at other sites in the body. Objective To examine, in a prospective study, the presence of synovitis in people with an increased risk of developing RA. Methods Thirteen people without evidence of arthritis, who were positive for IgM rheumatoid factor and/or anticitrullinated protein antibodies, were included in the study. To evaluate synovial inflammatory changes, all participants underwent dynamic contrast-enhanced MRI and arthroscopic synovial biopsy sampling of a knee joint at inclusion. Results were compared with knee MRI data and synovial biopsy data of 6 and 10 healthy controls, respectively. Results MRI findings evaluated by measurement of maximal enhancement, rate of enhancement, synovial volume and enhancement shape curve distribution were similar between the autoantibody-positive subjects and the healthy controls. Consistent with these findings, all but one autoantibody-positive subject showed very low scores for phenotypic markers, adhesion molecules and vascularity, all in the same range as those in normal controls. The one person with higher scores had patellofemoral joint space narrowing. Conclusion Subclinical inflammation of the synovium does not coincide with the appearance of serum autoantibodies during the pre-RA stage. Thus, systemic autoimmunity precedes the development of synovitis, suggesting that a ‘second hit’ is involved. This study supports the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.