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    Synovial tissue sublining CD68 expression is a biomarker of therapeutic response in rheumatoid arthritis clinical trials: consistency across centers.

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    Authors
    Bresnihan, Barry
    Pontifex, Eliza
    Thurlings, Rogier M
    Vinkenoog, Marjolein
    El-Gabalawy, Hani
    Fearon, Ursula
    Fitzgerald, Oliver
    Gerlag, Danielle M
    Rooney, Terence
    van de Sande, Marleen G
    Veale, Douglas
    Vos, Koen
    Tak, Paul-Peter
    Show allShow less
    Affiliation
    St. Vincent's University Hospital, Dublin, Ireland. barry.bresnihan@gmail.com
    Issue Date
    2012-02-01T10:29:17Z
    MeSH
    Antibodies, Monoclonal/therapeutic use
    Antibodies, Monoclonal, Murine-Derived
    Antigens, CD/*metabolism
    Antigens, Differentiation, Myelomonocytic/*metabolism
    Antirheumatic Agents/therapeutic use
    Arthritis, Rheumatoid/*drug therapy/metabolism/pathology
    Biological Markers/*metabolism
    Biopsy
    Clinical Trials as Topic/*methods/*standards
    Drug Monitoring/methods/standards
    Humans
    Macrophages/pathology
    Reproducibility of Results
    Synovial Membrane/metabolism/pathology
    Show allShow less
    
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    Citation
    J Rheumatol. 2009 Aug;36(8):1800-2.
    Journal
    The Journal of rheumatology
    URI
    http://hdl.handle.net/10147/207489
    DOI
    10.3899/jrheum.090348
    PubMed ID
    19671815
    Abstract
    OBJECTIVE: To determine whether the correlation between the mean change in disease activity and the mean change in synovial sublining (sl) CD68 expression could be demonstrated across different academic centers. METHODS: Synovial biopsies obtained at arthroscopy from patients with rheumatoid arthritis before and 160 days after rituximab therapy were selected and coded. Paired sections were processed independently at Amsterdam Medical Center (AMC) and at St. Vincent's University Hospital (SVUH), Dublin. Digital image analysis (DIA) was employed at both centers to quantify sublining CD68 expression. RESULTS: After analysis of CD68sl expression at centers in 2 different countries, high levels of intracenter and intercenter agreement were observed. For the pooled sections stained at AMC, the correlation between 2 investigators was R = 0.942, p = 0.000, and for sections stained at SVUH, R = 0.899, p = 0.001. Similarly, the intracenter correlations for DeltaCD68sl expression after treatment were R = 0.998, p = 0.000, for sections stained at AMC and R = 0.880, p = 0.000, for sections stained at SVUH. The intercenter correlation for the pooled scores of sections stained at AMC was R = 0.85, p = 0.000, and for the sections stained at SVUH, R = 0.62, p = 0.001. The consistent correlation between DeltaDAS (Disease Activity Score) and DeltaCD68sl expression across different studies (Pearson correlation = 0.895, p < 0.001) was confirmed. The standardized response mean values for DeltaCD68sl, calculated from analyses at both AMC and SVUH, were consistently 0.5 or greater, indicating a moderate to high potential to detect change. CONCLUSION: The correlation between mean DeltaDAS and mean DeltaCD68sl expression was confirmed across 2 centers. Examination of serial biopsy samples can be used reliably to screen for interesting biological effects at the site of inflammation at an early stage of drug development.
    Language
    eng
    ISSN
    0315-162X (Print)
    0315-162X (Linking)
    ae974a485f413a2113503eed53cd6c53
    10.3899/jrheum.090348
    Scopus Count
    Collections
    St. Vincent's University Hospital

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