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Expression of chemokines CXCL4 and CXCL7 in the synovium at an early stage of rheumatoid arthritis

Adlard, Nichola Jayne (2016)
Ph.D. thesis, University of Birmingham.

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Abstract

Identification of suitable biomarkers is growing increasingly important for the treatment of rheumatoid arthritis (RA). They can be measured in a number of different biological materials and can provide clinical information regarding prediction, diagnosis, and prognosis of disease, as well as response to therapeutics.

In this thesis, I utilised synovial biopsies collected from patients enrolled in the Birmingham Early Inflammatory Arthritis Cohort (BEACON) to test the hypothesis that detection of expression of CXCL4 and CXCL 7 may be used to predict progression of early stage synovitis to RA. I found that these two chemokines, CXCL4 and CXCL 7, were predominantly expressed on macrophages within the synovium of patients presenting with early synovitis. Increased CXCL4 and CXCL 7 was observed in patients with early RA compared to those with a resolving disease course. However, this increase was transient as expression in treatment naive established RA patients (>12 weeks duration, <3 years duration) was comparable
to uninflamed controls.

Moreover, I identified expression of a variant ofCXCL4, CXCL4Ll in the rheumatoid synovium. Expression of this potent inhibitor of angiogenesis was evident in the lining layer of the synovium.

These data highlight CXCL4 and CXCL 7 as potential predictors of disease outcome in patients presenting with early synovitis.

Type of Work:Ph.D. thesis.
Supervisor(s):Scheel-Toellner, Dagmar and Filer, Andrew (Dr)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Additional Information:

Publication resulting from research: Yeo, L., et al. "Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis." Annals of the rheumatic diseases (2015) http://dx.doi.org/10.1136/annrheumdis-2014-206921

Subjects:RC Internal medicine
Institution:University of Birmingham
ID Code:6600
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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