Cartilage biomarkers in ankylosing spondylitis: Relationship to clinical variables and treatment response

Kim, Tae‐Hwan; Stone, Millicent; Payne, Ursula; Zhang, Xiang; Ionescu, Mirela; Lobanok, Tatiana; King, Lindsay; Poole, A. Robin; Inman, Robert D.

doi:10.1002/art.20870

Cited by 47 publications

(27 citation statements)

References 19 publications

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“…A previous study of 23 patients with AS demonstrated elevated levels of CPII and 846 epitope in patients with concomitant peripheral synovitis, which supports this hypothesis (23). However, increased osteoclast activation has been documented in animal models of AS (35) and bone resorption markers are increased in AS, particularly in patients with active disease (36,37).…”

Section: Discussionmentioning

confidence: 59%

“…Some of these biomarkers have been shown to be sensitive and specific for early cartilage changes associated with isolated joint injury in an experimental model of osteoarthritis (OA) (22). A previous study showed that patients with AS demonstrated significant elevations in serum levels of CPII, the 846 epitope, and the CPII:C2C ratio, compared with normal controls (23).…”

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confidence: 99%

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

Maksymowych¹,

Landewé²,

Conner‐Spady³

et al. 2007

Arthritis & Rheumatism

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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

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 99%

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

Maksymowych¹,

Landewé²,

Conner‐Spady³

et al. 2007

Arthritis & Rheumatism

Self Cite

154

100

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“…MMP‐3 was selected as it degrades other minor proteins in tendon matrix, including collagens III, IV, IX, and X, and also proteoglycans and elastin 28, 29, 30, 31, 32, 33. The C1,2C (or COL 2 3/4C short) antibody detects the carboxy terminus of fragmented type I and II collagen, cleaved by collagenases MMP‐1, MMP‐8 or MMP‐13 21, 34, 35, 36, 37…”

Section: Methodsmentioning

confidence: 99%

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

Spiesz

Thorpe

Chaudhry

et al. 2015

Journal Orthopaedic Research

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The role of inflammation in tendon injury is uncertain and a topic of current interest. In vitro studies of tendon accelerated overload damage can serve as a valuable source of information on the early stages of tendinopathy. Viable fascicle bundles from bovine flexor tendons were subjected to cyclic uniaxial loading from 1–10% strain. Immuno‐staining for inflammatory markers and matrix degradation markers was performed on the samples after mechanical testing. Loaded samples exhibited visible extracellular matrix damage, with disrupted collagen fibers and fiber kinks, and notable damage to the interfascicular matrix. Inflammatory markers COX‐2 and IL‐6 were only expressed in the cyclically loaded samples. Collagen degradation markers MMP‐1 and C1,2C were colocalized in many areas, with staining occurring in the interfascicular matrix or the fascicular tenocytes. These markers were present in control samples, but staining became increasingly intense with loading. Little MMP‐3 or MMP‐13 was evident in control sections. In loaded samples, some sections showed intense staining of these markers, again localized to interfascicular regions. This study suggests that inflammatory markers may be expressed rapidly after tendon overload exercise. Interestingly, both inflammation and damage‐induced matrix remodeling seem to be concentrated in, or in the vicinity of, the highly cellular interfascicular matrix. © 2015 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. J Orthop Res 33:889–897, 2015.

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“…Biomarkers reflecting type II collagen degradation include Col2-3/4 (long mono) (C2C) and CTX-II. CPII, 846 epitope, and the CPII/C2C ratio have been reported as increased at baseline in AS, but only the CPII/C2C ratio correlated with CRP in patients receiving infliximab [25]. A decrease in C2C was shown to correlate with the reduction in CRP and ESR levels in patients receiving etanercept [24].…”

Section: Biomarkers Indirectly Reflecting Inflammationmentioning

confidence: 97%

Biomarkers in Spondyloarthritis

Maksymowych

2010

Curr Rheumatol Rep

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Key challenges in the management of spondyloarthritis focus on the lack of availability of measures of disease activity and the inability to predict joint damage or response to treatment, which is expensive and associated with potentially serious toxicity. Recent studies have focused on the possible contribution of soluble biomarkers, which have been selected based on current understanding of their role in inflammation and/or their association with turnover of joint matrix. Emerging candidates for disease activity markers include interleukin-6 and soluble cytotoxic T lymphocyte associated molecule-4. Potential predictors of damage include metalloproteinase-3 and sclerostin. Acute-phase reactants C-reactive protein and serum amyloid A and interleukin-6 are currently the best predictors of treatment response. Significant study limitations are small sample size and the lack of multivariate analyses that can determine whether the biomarker contributes information that is independent of other clinical and laboratory variables used in routine care.

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Cartilage biomarkers in ankylosing spondylitis: Relationship to clinical variables and treatment response

Cited by 47 publications

References 19 publications

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

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

Tendon extracellular matrix damage, degradation and inflammation in response to in vitro overload exercise

Biomarkers in Spondyloarthritis

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