Pathological processes involved in the initiation of rheumatoid
synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of
rheumatoid arthritis (RA) by assessing a panel of T cell, macrophage, and stromal cell related
cytokines and
chemokines in the synovial fluid of patients with early
synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory
arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute
crystal arthritis, established RA and
osteoarthritis.
Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23
cytokines and
chemokines measured using a multiplex based system. Patients with early inflammatory
arthritis who subsequently developed RA had a distinct but transient synovial fluid
cytokine profile. The levels of a range of T cell, macrophage and stromal cell related
cytokines (e.g. IL-2, IL-4,
IL-13, IL-17, IL-15,
basic fibroblast growth factor and
epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early
arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent
synovitis exhibited elevated levels of
interferon-gamma at initiation. Early
synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid
cytokine profile. The
cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA.