Markers of enhanced cartilage collagen metabolism found in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are detectable in serum samples, several of which are associated with disease activity and treatment response. These biomarkers may represent new diagnostic tests for PsA and AS, according to research published in Arthritis Research & Therapy.1

Spondyloarthropathies (SpAs) when left untreated can result in severe joint deformities secondary to alterations in cartilage and bone turnover.  A lack of classical pathognomonic features and serological diagnostic tests may contribute to morbidity associated with diagnostic delay.  

To assess the potential clinical utility of biochemical markers of cartilage and bone turnover, researchers in Copenhagen evaluated a cohort of patients from 3 rheumatology centers in Southern Denmark with axial spondyloarthritis (axSpA) and PsA, and measured markers of mature collagen IIB (Pro-C2) synthesis and turnover.


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Patients with axSpA (n=110) were diagnosed according to the Assessment of SpondyloArthritis international Society (ASAS) criteria and patients with PsA (n=101) were diagnosed according to the Classification of Psoriatic Arthritis (CASPAR) criteria.  Healthy controls (n=118) were identified from blood donors. Baseline demographics including body mass index (BMI), age, smoking status, alcohol consumption, and human leukocyte antigen (HLA)-B27 status were recorded.

High Yield Data Summary

  • Increases in hypertrophic chondrocyte activity in PsA and axSpA may yield measurable biochemical cartilage markers to aid assessment of disease activity

Disease activity was measured with the 68 swollen joint count, 68 tender joint count, Spondyloarthritis Research Consortium of Canada enthesitis index, Health Assessment Questionnaire (HAQ), visual analogue scale, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Disease Activity Score in 28 joints (DAS28), and Ankylosing Spondylitis Disease Activity Score (ASDAS).  

Nonfasting blood samples were subsequently taken for serum analysis. The competitive enzyme-linked immunosorbent assay (ELISA) was used to detect levels of Pro-C2. 

Increased levels of Pro-C2, reflecting mature collagen type IIB formation, were found in serum samples from patients with axSpA and PsA as compared to samples from healthy controls (axSpA Pro-C2 median concentration 1.11 ng/ml, 0.67–1. 64, PsA Pro-C2 (median concentration 1.03 ng/ml, 0.53–1.47, healthy controls Pro-C2 median concentration 0. 30 ng/ml, 0.16–0.41, P<0.0001). 

Furthermore, Pro-C2 levels were correlated with HAQ and Bath Ankylosing Spondylitis Functional Index (BASFI) scores in patients with axSpA receiving treatment with either biologic or synthetic disease-modifying antirheumatic drugs.  Pro-C2 also 2 correlated with ASDAS in patients with axSpA who were not receiving treatment.

“The [increases in] Pro-C2 levels may reflect an anabolic chondrocyte response to counterbalance increased collagen type II degradation in active disease”, the authors hypothesized. 

C-Col 10 levels, expressed by hypertrophic chondrocytes and representing type X collagen turnover, were significantly higher in patients with axSpA naive to tumor necrosis factor inhibitor (TNFi) therapy than in healthy controls (P=.008). This association with C-Col 10 was not found for patients with PsA.  These lower C-Col10 levels in patients with axSpA receiving TNFi treatment may be reflective of the targeting of hypertrophic chondrocytes in axSpA.

When comparing the axSpA and PsA cohorts to each other, there was no significant difference in either Pro-C2 or C-Col10.  ROC analysis revealed good discriminating power of both Pro-C2 and C-Col10 in differentiating patients with axSpA, PsA, and healthy controls. 

Summary and Clinical Applicability

Cartilage collagen metabolism is increased in axSpA and PsA, as evidenced by increased serum levels of Pro-C2 as compared to healthy controls.  Enhanced chondrocyte activity in axSpA and PsA may be reflected in certain biochemical cartilage markers, indicating active disease and/or response to treatment. 

Results from this study suggests that “the SpA-related type II collagen response of normal chondrocytes is preserved, while the collagen type X expression of cartilaginous and enthesopathic lesions is modified by TNFis”, the authors concluded.

Limitations and Disclosures

The definitive prognostic value of these biomarkers cannot be determined by the cross-sectional design of this study.

Study authors NSG, MAK, YH, ACBJ, and ASS were employed by Nordic Bioscience, a company specializing in biomarker development, during the study.

Reference

1. Gudmann NS, Munk HL, Christensen AF, et al. Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis. Arthritis Res Ther. 2016;18(1):141. doi: 10.1186/s13075-016-1040-z