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    Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study. 
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    • Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.
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    • William Harvey Research Institute
    • Centre for Experimental Medicine and Rheumatology (EMR)
    • Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.
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    Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.

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    Accepted Version (21.25Mb)
    Volume
    17
    Pagination
    58 - ?
    DOI
    10.1186/s13075-015-0567-8
    Journal
    Arthritis Res Ther
    Metadata
    Show full item record
    Abstract
    INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice.
    Authors
    Kelly, S; Bombardieri, M; Humby, F; Ng, N; Marrelli, A; Riahi, S; DiCicco, M; Mahto, A; Zou, L; Pyne, D
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/9883
    Collections
    • Centre for Experimental Medicine and Rheumatology (EMR) [349]
    Language
    eng
    Licence information
    http://www.arthritis-research.com/content/17/1/58/abstract
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