Use this URL to cite or link to this record in EThOS:
Title: Characterisation of cytokine expression in early synovitis and established rheumatoid arthritis
Author: Yeo, Lorraine
ISNI:       0000 0004 2719 5864
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2012
Availability of Full Text:
Access from EThOS:
Access from Institution:
In rheumatoid arthritis (RA), chronic inflammation and destruction of the joint is driven by local production of cytokines. My aims were to characterise cytokine mRNA expression in multiple synovial fluid cell populations in early and established RA and to study these, in addition to whole synovial tissue, in early synovitis patients in relation to disease outcome. I established a novel method to determine cytokine mRNA expression in synovial fluid CD4 T cells, CD8 T cells, B cells, macrophages and neutrophils directly ex vivo. I made several novel observations, for example RA synovial fluid B cells expressed high levels of RANKL. As RANKL drives bone resorption, this suggests a potential role for B cells in bone erosion in RA. RANKL protein was expressed by B cells in synovial tissue, and mainly by memory B cells in synovial fluid. Furthermore, synovial RANKL levels were reduced after treatment with the B cell depleting therapy, rituximab. Overall, both in whole synovial tissue and in sorted cells, the cytokine mRNA expression profile was very similar in early synovitis patients who subsequently developed RA or had resolving synovitis, and in patients with early or established RA. In comparison, cytokines and chemokines were upregulated in early and established arthritis patients compared to uninflamed controls. The finding that cytokine mRNA expression is largely similar in early synovitis patients who develop RA or have resolving disease, and in the early and established phases of RA, suggests that cytokine expression is reflective of general synovial inflammation, rather than being specific for early synovitis outcome or stage of RA.
Supervisor: Not available Sponsor: MRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QP Physiology ; QR180 Immunology ; RC Internal medicine