Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity

Abstract

Objective. To define variations in the cellular infiltrate and in the expression of monokines in synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations of disease and different levels of disease activity. Methods. The immunohistologic features of synovial biopsy specimens from 31 patients with early RA (<1 year) and 35 patients with longstanding RA (>5 years) were compared. The possible associations between these features and local disease activity, as measured by the score for pain in the biopsied knee joint, were also evaluated. Results. The immunohistologic features were not dependent on disease duration. We found a positive correlation between the scores for knee pain and the semiquantitative scores for the number of macrophages, as well as the expression of interleukin‐6 and tumor necrosis factor α, whereas the correlation with the scores for CD4+ T cells was negative. Multivariate analysis showed that these correlations were highly statistically significant (P < 0.003). Conclusion. The results do not support the view that inflammatory mechanisms in the synovial tissues of RA patients differ between early and late stages of the disease. The findings presented here are consistent with the concept that early RA is the result of a synovitis process of longer duration and that macrophage‐derived cytokines play an important role in maintaining the clinical signs of inflammation.

Rheumatoid arthritis is a heterogeneous disease: Evidence for differences in the activation of the STAT‐1 pathway between rheumatoid tissues

“…The combined analysis of cellular complexity, together with a comprehensive overview of the concomitant gene expression profile, provides opportunities for further research. The expression data suggest involvement of two distinct disease processes in rheumatoid pathogenesis, which is in accordance with data from several studies that indicated biologic heterogeneity in RA (6,19,33,34). The existence of a spectrum of molecular variation that may be translated into distinct pathophysiologic mechanisms at the site of the lesion would fit a model proposed by Firestein and Zvaifler (3), who suggested two processes in the destruction stage of RA.…”

“…The presence of such characteristic cell-specific gene clusters correlates with reported data on infiltration of mononuclear cells into the rheumatoid synovium (6,19,33,34). Overexpression of these gene clusters is consistent with increased ESRs.…”

“…The clinical presentation of RA may reveal striking heterogeneity, with a spectrum ranging from mild to severe disease. In addition, marked variability in the features of synovial inflammation among RA patients has been described (6)(7)(8). The wide variation in responsiveness to different modes of antirheumatic treatment is consistent with this notion (9,10).…”

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

“…T cells are thought to play a role in the induction phase of the disease, supporting the activation of collagen-specific B cells, but have a less No production of rheumatoid factor * RA ϭ rheumatoid arthritis; CIA ϭ collagen-induced arthritis; MHC ϭ major histocompatibility complex; NSAIDs ϭ nonsteroidal antiinflammatory drugs; PGIA ϭ proteoglycan-induced arthritis; AIA ϭ adjuvant-induced arthritis; SCW ϭ streptococcal cell wall; STIA ϭ serum transfer-induced arthritis; Tg ϭ transgenic; TNF ϭ tumor necrosis factor. (9), which is in contrast to RA synovium, where macrophages constitute the major phagocytic cell population (10). Cytokines influence disease induction and development in a time-dependent manner (2) ( Table 3).…”

“…IL-6 is abundantly expressed in both the synovial fluid and serum of patients with RA (102); its expression in synovial tissue is significantly correlated with clinical signs and symptoms of arthritis (10). It has a variety of functions, including initiation of the acute-phase response, activation of vascular endothelial cells, and induction of B cell and T cell differentiation (89,103).…”