Structural Progression of Ankylosing Spondylitis Associated with Elevation in Two NOVEL, Inflammatory Biomarkers; Matrix Metalloproteinase and Cathepsin-Derived

Anne C. Bay-Jensen¹, Morten Asser Karsdal², Stephanie Wichuk³, Zheng Zhao⁴, Robert GW Lambert⁵, Per Qvist⁶ and Walter P. Maksymowych⁷, ¹Cartilage Biomarkers and Research, Nordic Bioscience, Herlev, Denmark, ²Nordic Bioscience A/S, Herlev, Denmark, ³Medicine, University of Alberta, Edmonton, AB, Canada, ⁴Department of Rheumatology, University of Alberta and PLA General Hospital, Beijing, PR China, Beijing, AB, China, ⁵Radiology, University of Alberta, Edmonton, AB, Canada, ⁶Nordic Bioscience, Herlev, Denmark, ⁷Department of Medicine, University of Alberta, Edmonton, AB, Canada

Meeting: ACR/ARHP Annual Meeting 2012

Keywords: Ankylosing spondylitis (AS), biomarkers and matrix metalloproteinase (MMP), C Reactive Protein

Session Information

Title: Spondylarthritis and Psoriatic Arthritis - Pathogenesis, Etiology

Session Type: Abstract Submissions (ACR)

Background/Purpose: Current inflammatory biomarkers, such as CRP, have insufficient sensitivity and specificity to be broadly accepted for diagnosis and prognosis of AS. We hypothesized, that quantification of inflammation markers derived from the affected tissue might have improved clinical utility compared to the systemic markers. We developed two novel biomarker assays detecting MMP and cathepsin-derived CRP (MMP-CAT and CAT-CRP) and aimed to determine their diagnostic utility and association with radiological progression.

Methods: Serum samples (n=124) from AS patients, mean disease duration (SD) 18.0 (11.4) years were assessed. Within this cohort, samples from 16 AS patients with structural progression over two years and 29 without were selected for prognostic evaluation (sub-cohort 1A). A progressor was defined as having a baseline mSASSS of ≥ 10 units and progression of ≥5 units plus ≥ 1 new syndesmophyte over two years. Non-progressors were defined as disease duration at baseline of > 10 years, baseline mSASSS < 5 units, and no change in mSASSS over 2 years Sub-cohort 1B comprised samples from 53 AS patients pre- and post- anti-TNF treatment. We also included samples (n=39) from healthy controls.

Results: CRP-MMP and CRP-CAT were both elevated in AS compared to controls; mean (SD) 9.84 (4.40) ng/ml vs. 4.82 (1.49) ng/ml (p<0.05), respectively, for CRP-MMP, and 299.6 (137.6) ng/ml vs 178.6 (54.03) ng/ml (p<0.05), for CRP-CAT. AUC according to ROC analysis was 0.94 (p<0.0001) and 0.85 (p<0.0001) for CRP-MMP and CRP-CAT, respectively. In AS patients with progression CRP-MMP and CRP-CAT were significantly elevated compared to non-progressors. Both CRP-related markers decreased significantly after short term (2-3 months) anti-TNF treatment.

Conclusion: Both MMP and Cathepsin-derived fragments of CRP are significantly elevated in AS patients. These markers, but not CRP, were significantly elevated at baseline in patients having structural progression defined by a composite index including mSASSS and syndesmophyte quantification.

Disclosure:

A. C. Bay-Jensen,
None;

M. A. Karsdal,

Nordic Bioscience Diagnostic,

S. Wichuk,
None;

Z. Zhao,
None;

R. G. Lambert,
None;

P. Qvist,
None;

W. P. Maksymowych,
None.

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