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

Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 14:R127

First Online: 28 May 2012Received: 02 April 2012Revised: 10 May 2012Accepted: 28 May 2012


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.

AbbreviationsASankylosing spondylitis

BASDAIBath ankylosing spondylitis disease activity index

BASFIBath ankylosing spondylitis functional index

BAS-GBath ankylosing spondylitis global health

CRPC-reactive protein

ELISAenzyme-linked immunosorbent assay

HGFhepatocyte growth factor



MMPmatrix metalloproteinase

PCprincipal component

PCAprincipal component analysis

TIMPtissue inhibitor of metalloproteinase

TNFtumour necrosis factor

VEGFvascular endothelial growth factor.

Electronic supplementary materialThe online version of this article doi:10.1186-ar3857 contains supplementary material, which is available to authorized users.

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Author: Derek L Mattey - Jonathan C Packham - Nicola B Nixon - Lucy Coates - Paul Creamer - Sarah Hailwood - Gordon J Taylor -


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