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

Adlard, Nichola Jayne (2016). Expression of chemokines CXCL4 and CXCL7 in the synovium at an early stage of rheumatoid arthritis. University of Birmingham. Ph.D.

Preview

Adlard16PhD.pdf
PDF - Accepted Version
Download (6MB)

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:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):