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This article is part of the supplement: 25th European Workshop for Rheumatology Research

Poster presentation

Real-time quantitative PCR used as a biomarker for synovial gene expression after oral prednisolone therapy in patients with rheumatoid arthritis

DM Gerlag1, DL Boyle2, P Laud3, T Nash3, PP Tak1 and GS Firestein2

Author Affiliations

1 Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, The Netherlands

2 Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, La Jolla, California, USA

3 Astra Zeneca, Macclesfield, UK

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Arthritis Research & Therapy 2005, 7(Suppl 1):P161  doi:10.1186/ar1682


The electronic version of this article is the complete one and can be found online at:


Received:11 January 2005
Published:17 February 2005

© 2005 BioMed Central Ltd

Poster presentation

The objective of this study was to evaluate the use of real-time quantitative PCR (Q-PCR) using a cellular standard to detect changes in gene expression in synovial tissue samples that could potentially serve as such biomarkers correlating with clinical disease activity. Therefore, the effects of treatment with corticosteroids, a known effective therapy, were analyzed in patients with active rheumatoid arthritis. Patients were randomized to receive either oral prednisolone (n = 10, 60 mg daily for the first and 40 mg daily for the second week) or placebo (n = 11). All patients underwent an arthroscopic synovial biopsy procedure directly before and after 14 days of treatment. Real-time Q-PCR was used to quantify gene expression of tumour necrosis factor alpha, IL-1β, IL-6 and MMP-1 in the synovial tissue samples. The values were expressed as relative units compared with a cellular-based standard. Statistical analysis was performed using an analysis of covariance model. The mean DAS28 was 2.0 units lower (95% confidence interval, 1.0–3.0) after prednisolone therapy compared with placebo. The mean DAS28 (± standard deviation) decreased (from 6.27 ± 0.95 to 4.11 ± 1.43) after prednisolone therapy, but not in the placebo group. For gene expression of IL-8 and MMP-1, the estimated effect of prednisolone compared with placebo was large, and the confidence intervals excluded the likelihood of no effect. A clear trend towards reduction was seen in IL-β and tumour necrosis factor alpha mRNA expression in the prednisolone group, but confidence intervals included the value for no effect. The results of this study show that mRNA expression of IL-8 and MMP-1 quantified by Q-PCR may serve as biomarkers in small proof of principle trials designed to screen for potential efficacy in rheumatoid arthritis patients.

Acknowledgement

The clinical part of study was funded by Astra Zeneca, UK.