Open Access Research article

Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis

Derek L Mattey12*, Jonathan C Packham1, Nicola B Nixon1, Lucy Coates3, Paul Creamer4, Sarah Hailwood5, Gordon J Taylor3 and Ashok K Bhalla3

Author Affiliations

1 Haywood Rheumatology Centre, University Hospital of North Staffordshire, Stoke-on-Trent ST6 7AG, UK

2 Institute of Science and Technology in Medicine, Keele University, Keele ST5 5BG, UK

3 Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, UK

4 Department of Rheumatology, Southmead Hospital, Bristol BS10 5NB, UK

5 Department of Rheumatology, University Hospital of North Durham, Durham DH1 5TW, UK

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Arthritis Research & Therapy 2012, 14:R127  doi:10.1186/ar3857

Published: 28 May 2012

Abstract

Introduction

The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs.

Methods

Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression.

Results

Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index.

Conclusions

A profile consisting of high levels of MMP-8, MMP-9, hepatocyte growth factor and CXCL8 is associated with increased disease activity in AS. High MMP levels are also associated with smoking and worse function in AS.