Features of the Synovium of Individuals at Risk of Developing Rheumatoid Arthritis: Implications for Understanding Preclinical Rheumatoid Arthritis

Abstract

ObjectiveFindings from previous studies have suggested that subclinical inflammation of the synovium does not coincide with the appearance of rheumatoid arthritis (RA)–specific autoantibodies. This study was undertaken to examine the relationship between the presence of autoantibodies, changes in the synovium, and development of arthritis over time in a markedly larger, prospective study.MethodsFifty-five individuals who were IgM rheumatoid factor positive and/or anti–citrullinated protein antibody (ACPA) positive (detected by the anti–cyclic citrullinated peptide antibody test) and who were without any evidence of arthritis upon physical examination were included in the study. ACPAs were subsequently also detected using a multiplex chip-based assay. All individuals underwent magnetic resonance imaging and mini-arthroscopic synovial biopsy sampling of a knee joint at inclusion and were prospectively followed up. Proportional hazards regression analysis was performed to investigate whether changes in the synovium were associated with the onset of arthritis.ResultsFifteen individuals (27%) developed arthritis after a median followup time of 13 months (interquartile range 6–27 months; range 1–47 months). No overt synovial inflammation was observed, but CD3+ T cell numbers in the biopsy tissue showed a borderline association with subsequent development of clinically manifest arthritis (hazard ratio 2.8, 95% confidence interval [95% CI] 0.9–9.1; P = 0.088). In addition, the presence of CD8+ T cells was associated with ACPA positivity (odds ratio [OR] 16.0, 95% CI 1.7–151.1) and with the total number of ACPAs present (OR 1.4, 95% CI 1.0–1.8).ConclusionThese findings confirm and extend previous results showing the absence of clearcut synovial inflammation in individuals having systemic autoimmunity associated with RA. However, subtle infiltration by synovial T cells may precede the signs and symptoms of arthritis in preclinical RA.

Reply

“…The data presented by Air o and colleagues as well as the data derived from our own studies and those from other researchers, show shifts in CD81 T cell populations both in RA patients (6)(7)(8) and related animal models (9-11), and stress their dependence on disease activity and therapeutic strategy. CD81 T cell function and biology are garnering the greater attention of RA researchers, and these lymphocytes may prove to be valuable targets for future therapeutic and diagnostic strategies.…”

Synovial tissue research: a state-of-the-art review

“…91 A positive ACPA status in those with arthralgia is associated with the subsequent development of arthritis in only about 20-30% of these people after 30 months of follow up. 92,93 The synovial tissue of patients who are at risk of arthritis has also been examined in two relatively small studies Little evidence of synovitis was found in the first and subtle T-cell infiltration was noted in the second. 94 Data on alternative tissues such as lung and lymph node that may be important in the very early stages of arthritis as sites of first antigen presentation.…”

Predictive value of anti-citrullinated peptide antibodies: a real life experience

“…Anti-CCP antibodies and anti-citrullinated filaggrin antibodies are locally produced in inflamed joints; citrullinated fibrin is found in the synovia of patients with RA, and interestingly citrullinated proteins were extracted from lungs of patients with chronic obstructive pulmonary disease [53][54][55][56][57][58][59].…”