Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis

Abstract

Background: Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. There is a need for biomarkers reflecting core disease pathways for diagnosis and disease mapping. Pro-C2 reflects mature cartilage collagen type IIB formation, while C-Col10 represents turnover of type X collagen, which is exclusively expressed by hypertrophic chondrocytes. The objectives of this study were to study cartilage metabolism in axSpA and PsA by assessing Pro-C2 and C-Col10 and to evaluate their diagnostic utility against a healthy reference population.

Methods: Patients with PsA (n = 101) or axSpA (n = 110) were recruited consecutively from three rheumatology outpatient clinics. Demographic and clinical disease measures were recorded. Pro-C2 and C-Col10 were quantified in serum by using newly developed and specific competitive enzyme-linked immunosorbent assays based on monoclonal antibodies. One-way analysis of variance and Tukey's multiple comparison tests were performed on log-transformed data. ROC curve analysis was carried out to evaluate their discriminative power.

Results: Pro-C2 levels in serum were significantly increased in both axSpA (median concentration 1.11 ng/ml, 0.67-1.64) and PsA (median concentration 1.03 ng/ml, 0.53-1.47) compared with healthy controls (median concentration 0.30 ng/ml, 0.16-0.41) (p < 0.0001). Pro-C2 did not differ according to treatment. C-Col10 was slightly but equally elevated in the PsA and axSpA groups vs. the control group, but it was significantly lower in patients with axSpA undergoing tumor necrosis factor-α inhibitor (TNFi) treatment. ROC curve analysis revealed AUCs of 0.85 (95 % CI 0.79-0.89) for axSpA and 0.81 (95 % CI 0.75-0.86) for PsA.

Conclusions: These findings indicate that cartilage collagen metabolism was enhanced in the axSpA and PsA groups compared with the healthy control group. The lower C-Col10 level in patients with axSpA undergoing TNFi treatment may reflect that hypertrophic chondrocytes in axSpA are targeted by TNFi. ROC curve analysis showed a diagnostic potential for Pro-C2 in axSpA and PsA.

Keywords: C-Col10; Pro-C2; Psoriatic arthritis; Spondyloarthritis; Type II collagen; Type X collagen.

Fig. 1

a Pro-C2 was significantly increased in the axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) groups compared with the healthy control group. b C-Col 10 concentrations were slightly but significantly higher in the PsA group compared with the healthy control group. Error bars are shown as SEM. One-way analysis of variance was performed for intergroup comparisons. *p < 0.05, ****p < 0.0001

Fig. 2

Pro-C2 was significantly lower in patients with axial spondyloarthritis (axSpA) who were positive for the human leukocyte antigen (HLA)-B27 gene compared with the HLA-B27-negative patients. In patients with psoriatic arthritis (PsA), Pro-C2 did not differ significantly according to HLA-B27 status (p=0.31). Error bars are shown as SEM. Student’s t test was applied to compare the two groups. *p < 0.05. ns not significant

Fig. 3

C-Col10 was significantly higher in patients with axial spondyloarthritis (axSpA) naïve to biological treatment than in those currently or formerly treated with biologic DMARDs. The same trend was observed in patients with psoriatic arthritis (PsA), though it did not reach statistical significance. Error bars are shown as SEM. Student’s t test was applied to compare the two groups. *p < 0.05. ns not significant

Fig. 4

ROC analysis of (a) Pro-C2 in the axial spondyloarthritis (axSpA) group vs. the healthy control group, (b) Pro-C2 in the psoriatic arthritis (PsA) group vs. the healthy control group, (c) C-Col10 levels in the axSpA group vs. the healthy control group, and (d) C-Col10 in the PsA group vs. the healthy control group