TY - JOUR
T1 - Different stages of rheumatoid arthritis
T2 - Features of the synovium in the preclinical phase
AU - Van De Sande, M. G.H.
AU - De Hair, M. J.H.
AU - Van Der Leij, C.
AU - Klarenbeek, P. L.
AU - Bos, W. H.
AU - Smith, M. D.
AU - Maas, M.
AU - De Vries, N.
AU - Van Schaardenburg, D.
AU - Dijkmans, B. A.C.
AU - Gerlag, D. M.
AU - Tak, P. P.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=79953300919&partnerID=8YFLogxK
U2 - 10.1136/ard.2010.139527
DO - 10.1136/ard.2010.139527
M3 - Article
C2 - 21177292
AN - SCOPUS:79953300919
VL - 70
SP - 772
EP - 777
JO - Annals of the Rheumatic Diseases
JF - Annals of the Rheumatic Diseases
SN - 0003-4967
IS - 5
ER -