RT Journal Article
SR Electronic
T1 Different stages of rheumatoid arthritis: features of the synovium in the preclinical phase
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 772
OP 777
DO 10.1136/ard.2010.139527
VO 70
IS 5
A1 M G H van de Sande
A1 M J H de Hair
A1 C van der Leij
A1 P L Klarenbeek
A1 W H Bos
A1 M D Smith
A1 M Maas
A1 N de Vries
A1 D van Schaardenburg
A1 B A C Dijkmans
A1 D M Gerlag
A1 P P Tak
YR 2011
UL http://ard.bmj.com/content/70/5/772.abstract
AB 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.