Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: A two‐year prospective study (the DAMAGE study cohort)

作者：Bruce Kirkham, Marissa Lassere, John Edmonds, Katherine M. Juhasz, Paul Bird, C. Soon Lee, Ron Shnier, Ian Portek · 发表于：Arthritis & Rheumatism · 年份：2006 · DOI：10.1002/art.21749 · 被引用次数：339 · 研究领域：Rheumatoid Arthritis Research and Therapies、Spondyloarthritis Studies and Treatments、Musculoskeletal synovial abnormalities and treatments

OBJECTIVE: The primary aim of this prospective 2-year study was to explain the wide variability in joint damage progression in patients with rheumatoid arthritis (RA) from measures of pathologic changes in the synovial membrane. METHODS: Patients underwent clinical measurements and joint damage assessments by magnetic resonance imaging (MRI) and radiography at enrollment and at year 2. Synovial membrane was obtained by knee biopsy and assessed histologically by hematoxylin and eosin staining. Interleukin-1beta (IL-1beta), IL-10, IL-16, IL-17, RANKL, tumor necrosis factor alpha (TNFalpha), and interferon-gamma (IFNgamma) messenger RNA (mRNA) expression was determined by quantitative reverse transcription-polymerase chain reaction. The relationship of synovial measurements to joint damage progression was determined by multivariate analysis. RESULTS: Sixty patients were enrolled. Histologic features had no relationship to damage progression. Multivariate analysis by several different methods consistently demonstrated that synovial membrane mRNA levels of IL-1beta, TNFalpha, IL-17, and IL-10 were predictive of damage progression. IL-17 was synergistic with TNFalpha. TNFalpha and IL-17 effects were most pronounced with shorter disease duration, and IL-1beta effects were most pronounced with longer disease duration. IFNgamma was protective. These factors explained 57% of the MRI joint damage progression over 2 years. CONCLUSION: We have demonstrated for the first time in a prospect...