A multiparameter approach to monitor disease activity in collagen-induced arthritis.
BACKGROUND
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.
Seeuws
Sylvie
S
Department of Rheumatology, Ghent University, De Pintelaan 185, Ghent, 9000, Belgium. Sylvie.Seeuws@ugent.be
Jacques
Peggy
P
Van Praet
Jens
J
Drennan
Michael
M
Coudenys
Julie
J
Decruy
Tine
T
Deschepper
Ellen
E
Lepescheux
Lien
L
Pujuguet
Philippe
P
Oste
Line
L
Vandeghinste
Nick
N
Brys
Reginald
R
Verbruggen
Gust
G
Elewaut
Dirk
D
D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002356:Cartilage / Q000000981:diagnostic imaging; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D051379:Mice; D008811:Mice, Inbred DBA; D012044:Regression Analysis; D055114:X-Ray Microtomography / Q000379:methods*
D001323:Autoantibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D003094:Collagen; D019278:Matrix Metalloproteinase 3