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

[摘要] 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.

[发布机构] University:University of Birmingham;Department:School of Immunity and Infection

[关键词] R Medicine;RC Internal medicine