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Open Access Research article

A multiparameter approach to monitor disease activity in collagen-induced arthritis

Sylvie Seeuws1, Peggy Jacques1, Jens Van Praet1, Michael Drennan1, Julie Coudenys1, Tine Decruy1, Ellen Deschepper2, Lien Lepescheux3, Philippe Pujuguet3, Line Oste3, Nick Vandeghinste3, Reginald Brys3, Gust Verbruggen1 and Dirk Elewaut1*

Author Affiliations

1 Laboratory for Molecular Immunology and Inflammation, Department of Rheumatology, Ghent University, De Pintelaan 185, Ghent, 9000, Belgium

2 Biostatistics Unit, Ghent University, De Pintelaan 185, Ghent, 9000, Belgium

3 Galapagos NV, Generaal De Wittelaan L11 A3, Mechelen, 2800, Belgium

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Arthritis Research & Therapy 2010, 12:R160  doi:10.1186/ar3119

Published: 23 August 2010

Abstract

Introduction

Disease severity in collagen-induced arthritis (CIA) is commonly assessed by clinical scoring of paw swelling and histological examination of joints. Although this is an accurate approach, it is also labour-intensive and the application of less invasive and less time-consuming methods is of great interest. However, it is still unclear which of these methods represents the most discriminating measure of disease activity.

Methods

We undertook a comparative analysis in which different measurements of inflammation and tissue damage in CIA were studied on an individual mouse level. We compared the current gold standard methods - clinical scoring and histological examination - with alternative methods based on scoring of X-ray or micro-computed tomography (CT) images and investigated the significance of systemically expressed proteins, involved in CIA pathogenesis, that have potential as biomarkers.

Results

Linear regression analysis revealed a marked association of serum matrix metalloproteinase (MMP)-3 levels with all features of CIA including inflammation, cartilage destruction and bone erosions. This association was improved by combined detection of MMP-3 and anti-collagen IgG2a antibody concentrations. In addition, combined analysis of both X-ray and micro-CT images was found to be predictive for cartilage and bone damage. Most remarkably, validation analysis using an independent data set proved that variations in disease severity, induced by different therapies, could be accurately represented by predicted values based on the proposed parameters.

Conclusions

Our analyses revealed that clinical scoring, combined with serum MMP-3, anti-collagen IgG2a measurement and scoring of X-ray and micro-CT images, yields a comprehensive insight into the different aspects of disease activity in CIA.