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Abstract Number: 629

Biomarkers of Chondrocyte Activity Are Increased in Psoriasis Arthritis and Spondyloarthritis

Natasja Stæhr Gudman1, Heidi Lausten Munk2, Anne Friesgaard Christensen3, Leif Ejstrup4, Grith Lykke Sørensen5, Anne Gitte Loft3, Morten A. Karsdal6, Anne C. Bay-Jensen7, Yi He8, Anne Sofie Siebuhr9 and Peter Junker2, 1Nordic Bioscience, Biomarkers and Research, Herlev, Denmark, 2Department of Rheumatology, Odense University Hospital, Odense, Denmark, 3Department of Rheumatology, Vejle Hospital, Vejle, Denmark, 4Department of Rheumatology, Esbjerg Hospital, Esbjerg, Denmark, 5Cardiovascular and Renal Research, Institute of Molecular Medicin, University of Southern Denmark, Odense, Denmark, 6Research & Development, Nordic Bioscience, Biomarkers and Research, Herlev, Denmark, 7Cartilage Biomarkers and Research, Nordic Bioscience, Herlev, Denmark, 8Nordic Bioscience, Herlev, Denmark, 9Rheumatology, Nordic Bioscience, Biomarkers and Research, Herlev, Denmark

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biomarkers, cartilage, Collagen, psoriatic arthritis and spondylarthropathy

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Session Information

Session Title: Spondyloarthropathies and Psoriatic Arthritis - Pathogenesis, Etiology

Session Type: Abstract Submissions (ACR)

Background/Purpose: Psoriasis arthritis (PsA) and spondyloarthritis (SpA) are both inflammatory joint diseases in which the pathogenesis is not fully understood. However, both pathologies are associated with extracellular matrix (ECM) remodeling favoring cartilage formation and calcification (type II and X collagen formation) in the affected joints. Treatment of the diseases has improved within recent years, but the therapeutic response at the level of the individual cannot be adequately predicted. Hence, there is an increasing interest in diagnostic and prognostic biomarkers to further characterize the patients to achieve personalized medicine. The biomarker ProC2 measures the level of propeptide type II collagen and C-Col10 measures type X collagen. Collagen type X is exclusively expressed by hypertrophic chondrocytes and is a measure of hypertrophic cartilage. The aim of this study was to evaluate the level of two novel biomarkers of cartilage formation (ProC2) and hypertrophy (C-Col10) in SpA, PsA and healthy controls, and to investigate whether these markers would have diagnostic potential.

Methods: 99 PsA patients, 94 SpA patients and 120 age-matched healthy controls were included in the study. Demographic and clinical disease measures were recorded. ProC2 and C-Col10 were quantified in serum by newly developed and specific competitive ELISAs based on monoclonal antibodies. One way analysis of variance and Tukeys multiple comparison test were performed on log-transformed data. Receiver operator characteristics (ROC) curve analysis was carried out to evaluate the discriminative power of the biomarkers.

Results: The serum levels of P2BNP had a mean level of 0.59ng/ml for healthy controls, but were significantly increased in patients with either SpA (mean 1.25ng/ml) or PsA (mean 1.35) compared to controls (p<0.001). When segregating between  patients and healthy controls by mean of ROC curves the AUC was 0.78 for SpA (Cl 95% 0.71 to 0.84) and 0.79 (CI 95% 0.73-0.85) for PsA as listed at the table below. Furthermore SpA had a slightly, but significantly increased level of type X collagen (mean 0.60ng/ml) compared the controls (mean 0.56ng/ml) (p=0.035). None of the two markers correlated with age, sex, BMI and the markers did not correlate with each other.       

Conclusion: These findings indicate that both SpA and PsA arthritis have enhanced cartilage formation reflected by increased levels of PIIBNP levels in serum compared to healthy controls. In addition, an increased level of the hypertrophic chondrocyte collagen X marker was found in SpA only, indicating a difference in cartilage turnover between the two diseases. This difference could aid in the differentiation between SpA and PsA.

 

The AUC, sensitivity and specificity of each ROC-analysis

AUC (CI95%)

Sensitivity

Specificity

P2BNP

Healthy vs PsA

0.793 (0.73-0.85)

65.1

81.7

Healthy vs SpA

0.776 (0.71-0.84)

60.4

83.3

SpA vs. PsA

0.539 (0.46-0.62)

40.4

60.4

Col X

Healthy vs PsA

0.607 (0.53-0.68)

48.5

60.6

Healthy vs SpA

0.580 (0.50-0.66)

48.6

60.6

SpA vs. PsA

0.525 (0.45-0.60)

40.4

60.6

 


Disclosure:

N. S. Gudman,

Nordic Bioscience Diagnostic,

3;

H. L. Munk,
None;

A. F. Christensen,
None;

L. Ejstrup,
None;

G. L. Sørensen,
None;

A. G. Loft,
None;

M. A. Karsdal,

Nordic Bioscience Holding,

1,

Nordic Bioscience Diagnostic,

3;

A. C. Bay-Jensen,

Nordic Bioscience Diagnostic,

1;

Y. He,

Nordic Bioscience Diagnostic,

3;

A. S. Siebuhr,

Nordic Bioscience A/S,

3;

P. Junker,
None.

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