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Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

Increased apoptosis level in late stages of rheumatoid arthritis correlates with macrophage number

Introduction

Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by synovial hyperplasia and excessive mononuclear infiltration. Altered apoptosis was proposed as a possible mechanism for cell accumulation. In vitro experiments showed that monokines are able to inhibit synovial apoptosis in a dose dependent manner. In this study we aim to investigate synovial apoptosis with respect to disease duration, inflammatory cell type and monokines expression.

Materials and methods

Synovial biopsy speciments from eleven patients with longstanding RA (mean disease duration 21 years) and eight with early RA (mean disease duration 5 months) have been investigated. Samples were evaluated for apoptosis (TUNEL method combined with morphologic analysis), cell surface markers (CD3, CD68) and monkine expression (IL1α, IL1β, TNFα and IL6). Tissue sections were then microscopically analysed using comput-erised image analysis. Statistical analysis was done using Mann-Withney test, Spearman correlation test and linear regression.

Results

Apoptosis level in RA synovium is signficiantly higher in late cases compared with early ones (P = 0,001), while macrophage population significantly decreases during disease progession (P = 0,003). Macrophage score is negatively correlated with apoptosis level (R=-0,618; P = 0,0088). In contrast, no correlation could be observed between apoptosis and monokine expression or T cell score.

Discussion

Low level of apoptosis in early RA cases suggests an ineffective cell death mechanism that ultimately contributes to cell accumulation into the joint and propagation of the inflammatory response. Apoptosis is restored during disease progression, in parallel with a decrease of the macrophage number. These findings suggest apoptosis as a possible marker for early RA and a promising therapy target.

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Catrina, A., Ulfgren, A., Gröndal, L. et al. Increased apoptosis level in late stages of rheumatoid arthritis correlates with macrophage number. Arthritis Res Ther 3, P111 (2001). https://doi.org/10.1186/ar280

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Keywords

  • Rheumatoid Arthritis
  • Disease Duration
  • Cell Accumulation
  • Spearman Correlation Test
  • Cell Death Mechanism