Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Multiplex Assay of a Panel of 58 Biomarkers in Ankylosing Spondylitis: Identification of High Priority Candidates for Prediction of Structural Damage.
Maksymowych4, Walter P., Morency4, Nathalie, Wichuk4, Stephanie, Rahman1, Proton, Gladman2, Dafna D., Inman3, Robert D.
Radiographic progression in ankylosing spondylitis (AS) requires 2 years before it can be reliably detected and prospective studies have consistently identified only baseline radiographic damage as an independent predictor of radiographic progression in AS. This presents a major challenge to the study of disease modifying therapies and to the identification of patients at risk for damage progression. We aimed to simultaneously analyze a large panel of serologic biomarkers reflecting pathophysiological processes in AS as potential predictors of radiographic progression.
We used multiplexed sandwich immunoassays (Eve Technologies) to simultaneously quantify a panel of 58 biomarkers that comprised 8 markers reflecting bone turnover, calcium homeostasis and osteoclasis, 8 metalloproteinases (MMP), 6 joint tissue growth factors, 23 cytokines known to regulate inflammation, 9 chemokines, and 4 factors reflecting miscellaneous immunological processes such as T-cell co-stimulation and enthothelial activation. Serum was obtained at a single time point from 60 patients with AS and 60 age- and sex-matched controls. Selection of 30 AS patients was based on phenotypic characterization of their progression status as measured by the modified Stoke AS Spine Score (mSASSS) after patients had been followed for at least 2 years. Progressors were defined as those patients where the baseline mSASSS was at least 10 units, progression over 2 years was at least 5 units, and included at least one new syndesmophyte. Non-progressors were patients meeting all 3 of the following: disease duration at baseline of at least 10 years, baseline mSASSS of less than 5 units, and no change in mSASSS over 2 years. Unpaired t-test analyses were stratified according to radiographic phenotype.
A total of 23 biomarkers demonstrated significant differences between AS patients and controls, the most significant being osteocalcin and Rantes (both p<0.0001). Ten biomarkers only demonstrated significant differences from controls when analysis was stratified according to radiographic phenotype: in the progressor subgroup MMP-9, transforming growth factor alpha, and tumor necrosis factor alpha were significantly elevated compared to controls (all p<0.0001) while eotaxin, interferon alpha-2, and monocyte chemotactic protein-3 were significantly increased in the non-progressor subgroup. Three biomarkers, interleukin-17, interferon-gamma, and macrophage inhibitory protein-beta, demonstrated significantly increased levels in AS patients that were further increased in the progressor subgroup. Six biomarkers were significantly increased only in male patients and particularly the progressor subgroup, especially macrophage derived chemokine and CD40 ligand (both p<0.0001).
Multiplexed assay of an extensive panel of biomarkers reflecting pathophysiological processes implicated in AS has identified several biomarkers as high priority candidates for prospective validation studies aimed at predictors of structural damage in AS.
To cite this abstract, please use the following information:
Maksymowych, Walter P., Morency, Nathalie, Wichuk, Stephanie, Rahman, Proton, Gladman, Dafna D., Inman, Robert D.; Multiplex Assay of a Panel of 58 Biomarkers in Ankylosing Spondylitis: Identification of High Priority Candidates for Prediction of Structural Damage. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1451