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Abstract
Objectives
To define synovial apoptosis with respect to disease duration, inflammatory cell type,
FLIP (FLICE like inhibitory protein) and cytokines expression in patients with rheumatoid
arthritis (RA).
Methods
Synovial biopsy specimens from eleven patients with longstanding RA (median disease
duration 21 years) and eight with early RA (median disease duration 5 months) have
been investigated. We evaluated apoptosis (TUNEL method combined with morphologic
analysis), cell surface markers (CD3, CD68), cytokines (IL-1α, IL-1β, TNF-α and IL-6)
and FLIP expression. Computer-assisted image analysis was used for quantification.
Results
Apoptosis level in RA synovium was significantly higher in the group of patients with
long standing RA than in the patients with early RA (8.8% versus 0.6%, P = 0.001),
while number of macrophages and FLIP expression were higher in the early as compared
with long standing RA group (16.2% versus 8.3%, P = 0.02 and 31.1% versus 0.2%, P
= 0.001 respectively). All three markers significantly correlate with disease duration
(r = -0.7, P < 0.001 for FLIP, r = 0.6, P = 0.001 for apoptosis and r = -0.5, P <
0.05 for CD68). Cytokine expression and T cell scores were not significantly different
in early RA compared to longstanding RA. We did not observe differences between corticosteroids
treated versus corticosteroids non-treated patients or between DMARD treated versus
non-treated patients.
Conclusions
Our findings suggest that RA synovial macrophages are resistant to apoptosis in early
RA and express high levels of FLIP. During natural or drug modified disease progression
the apoptotic mechanism may be restored with a specific increase of synovial apoptosis
in patients with long standing arthritis.