Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis

Abstract

Objective. In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS.Methods. We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS).Results. Complete data were available on 97 patients. Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression. After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression (␤ ‫؍‬ 0.29, P ‫؍‬ 0.004). Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5-138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R 2 ‫؍‬ 50%). MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units).Conclusion. These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.Ankylosing spondylitis (AS) is characterized by the presence of inflammation in the spine and the development of ankylosis in the facet joints and intervertebral discs, which leads to immobility and functional impairment. The degree and rate of progression of radiographic changes can be reliably assessed using a validated scoring method, the modified Stoke AS Spine Score (mSASSS), which records structural changes in

Histopathological changes in supraspinous ligaments, ligamentum flava and paraspinal muscle tissues of patients with ankylosing spondylitis

“…25 Indeed, Maksymowych et al suggest that serum MMP-3 is an independent predictor of structural damage progression in patients with AS. 9 However, Wendling et al…”

“…7,8 Serum MMP-3, a key enzyme in ECM remodeling, is strongly elevated in AS patients. 9,10 Increased turnover of several different MMP-derived collagen species has been accepted as a main feature of AS. 11 Transforming growth factor-b1 (TGF-b1), the major form of TGF-b expressed in the immune system, is a multifunctional cytokine that plays a critical role in inflammation.…”

Circulating Citrullinated Vimentin Fragments Reflect Disease Burden in Ankylosing Spondylitis and Have Prognostic Capacity for Radiographic Progression

“…In a logistic regression model that included this VICM level of 7.2 nmoles/liter as a dichotomous independent variable, VICM was a significant predictor of 2-year progression in the mSASSS after adjustment for age, sex, disease duration, and baseline mSASSS ( Table 4). We next investigated whether a combination of baseline VICM level and baseline mSASSS could be an even stronger predictor of progression, using a previously reported methodology (23). Patients were divided into 2 groups: low baseline radiographic damage (mSASSS Ͻ10) and high baseline radiographic damage (mSASSS Ն10), and the prognostic ability of VICM at the 7.2 nmoles/liter cutoff derived from ROC analysis was further tested within these 2 groups.…”

Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers

“…], for example, MMP3 is significantly associated with this endpoint and it is now under further evaluation 54,55,56,57,58 . Among imaging techniques, ultrasound was considered an interesting candidate for assessing SpA enthesitis as a marker of inflammatory activity both at site specific (entheses) and patient levels 59,60,61,62,63 .…”