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For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis.Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor.A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68(+) macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritisTaken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA.

Original publication

DOI

10.1136/annrheumdis-2014-206921

Type

Journal article

Journal

Annals of the rheumatic diseases

Publication Date

04/2016

Volume

75

Pages

763 - 771

Addresses

Rheumatology Research Group, Centre for Translational Inflammation Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Keywords

Synovial Membrane, Macrophages, Humans, Arthritis, Rheumatoid, Disease Progression, Platelet Factor 4, beta-Thromboglobulin, von Willebrand Factor, Platelet Membrane Glycoprotein IIb, RNA, Messenger, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Cytokines, Fluorescent Antibody Technique, Immunohistochemistry, Reverse Transcriptase Polymerase Chain Reaction, Adult, Aged, Middle Aged, Female, Male, Real-Time Polymerase Chain Reaction, Machine Learning