Abstract
Synovial leukocyte apoptosis is inhibited in established rheumatoid arthritis (RA). In contrast, high levels of leukocyte apoptosis are seen in self-limiting crystal arthritis. The phase in the development of RA at which the inhibition of leukocyte apoptosis is first apparent, and the relationship between leukocyte apoptosis in early RA and other early arthritides, has not been defined. We measured synovial fluid leukocyte apoptosis in very early arthritis and related this to clinical outcome. Synovial fluid was obtained at presentation from 81 patients with synovitis of ≤ 3 months duration. The percentages of apoptotic neutrophils and lymphocytes were assessed on cytospin preparations. Patients were assigned to diagnostic groups after 18 months follow-up. The relationship between leukocyte apoptosis and patient outcome was assessed. Patients with early RA had significantly lower levels of neutrophil apoptosis than patients who developed non-RA persistent arthritis and those with a resolving disease course. Similarly, lymphocyte apoptosis was absent in patients with early RA whereas it was seen in patients with other early arthritides. The inhibition of synovial fluid leukocyte apoptosis in the earliest clinically apparent phase of RA distinguishes this from other early arthritides. The mechanisms for this inhibition may relate to the high levels of anti-apoptotic cytokines found in the early rheumatoid joint (e.g. IL-2, IL-4, IL-15 GMCSF, GCSF). It is likely that this process contributes to an accumulation of leukocytes in the early rheumatoid lesion and is involved in the development of the microenvironment required for persistent RA.
Highlights
Inhibition of T-cell apoptosis in the synovium of patients with established rheumatoid arthritis (RA) was first described in 1995 [1]
We recently showed that patients with very early RA, within the first 3 months of symptom onset, have a synovial fluid cytokine profile that is distinct from those of patients with other forms of very early synovitis and of patients with established RA [7]
Patients Synovial fluid was obtained at presentation from 81 patients with very early inflammatory arthritis
Summary
Inhibition of T-cell apoptosis in the synovium of patients with established rheumatoid arthritis (RA) was first described in 1995 [1]. The phenotype of rheumatoid synovial T cells (Bcl-XL high, Bcl-2low) demonstrated that their survival was maintained by stromal mechanisms rather than by the common γ-chain cytokines, and IFN-β was identified as a key fibroblastderived survival signal [3]. In addition to their effects on T cells, both IFN-β and synovial fluid from RA patients delay neutrophil apoptosis [4,5]. The synovial fluid of patients with very early RA is char-
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