Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin |
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Authors: | Email author" target="_blank">Karim?RazaEmail author Francesco?Falciani S?John?Curnow Emma?J?Ross Chi-Yeung?Lee Arne?N?Akbar Janet?M?Lord Caroline?Gordon Christopher?D?Buckley Mike?Salmon |
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Institution: | (1) MRC Centre for Immune Regulation, Division of Immunity and Infection, The University of Birmingham, Birmingham, UK;(2) Department of Rheumatology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK;(3) School of Biosciences, The University of Birmingham, Birmingham, UK;(4) Department of Radiology, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK;(5) Department of Immunology and Molecular Pathology, Royal Free, University College Medical School, London, UK |
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Abstract: | 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-γ 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. |
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