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

Derek Mattey, Jonathan Packham, Nicol Nixon, Lucy Coates, Paul Creamer, Sarah Hailwood, G J Taylor, Ashok Bhalla

Research output: Contribution to journalArticle

37 Citations (Scopus)
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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.
Original languageEnglish
Article numberR127
Number of pages10
JournalArthritis Research & Therapy
Volume14
Issue number3
Early online date28 May 2012
DOIs
Publication statusPublished - 2012

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Ankylosing Spondylitis
Matrix Metalloproteinases
Cytokines
Baths
Matrix Metalloproteinase 8
Hepatocyte Growth Factor
Biomarkers
Matrix Metalloproteinase 9
Principal Component Analysis
C-Reactive Protein
Cluster Analysis
Smoking
Tissue Inhibitor of Metalloproteinases
Logistic Models
Pathology
Technology

Cite this

Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis. / Mattey, Derek; Packham, Jonathan; Nixon, Nicol; Coates, Lucy; Creamer, Paul; Hailwood, Sarah; Taylor, G J; Bhalla, Ashok.

In: Arthritis Research & Therapy, Vol. 14, No. 3, R127, 2012.

Research output: Contribution to journalArticle

Mattey, D, Packham, J, Nixon, N, Coates, L, Creamer, P, Hailwood, S, Taylor, GJ & Bhalla, A 2012, 'Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis', Arthritis Research & Therapy, vol. 14, no. 3, R127. https://doi.org/10.1186/ar3857
Mattey, Derek ; Packham, Jonathan ; Nixon, Nicol ; Coates, Lucy ; Creamer, Paul ; Hailwood, Sarah ; Taylor, G J ; Bhalla, Ashok. / Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis. In: Arthritis Research & Therapy. 2012 ; Vol. 14, No. 3.
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AU - Hailwood, Sarah

AU - Taylor, G J

AU - Bhalla, Ashok

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AB - IntroductionThe 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. MethodsMeasurement 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. ResultsPrincipal 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. ConclusionsA 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.

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