Collagen triple helix repeat-containing 1 protein: an emerging biomarker and its influence on the clinical and sonographic disease severity in Egyptian medicated female rheumatoid arthritis patients

Abstract
Background
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease of synovial joints, with a multifactorial etiology. Collagen triple helix repeat-containing 1 protein (CTHRC1) is a biomarker produced by fibroblast-like synoviocytes, which was shown to be highly expressed in RA patients. The study aimed to measure serum CTHRC1 level in female RA patients currently on medical treatment and its influence on the clinical and sonographic severity of the disease.

Results
The patients’ mean age was 43.39 ± 8.55 years and median RA disease duration of 5.5 (0.33–20) years. RA patients showed significantly higher serum CTHRC1 level [89.71 ng/ml (53.95–353.45)] in comparison to controls [87.38 ng/ml (44.47–110.3)] (U = 430, P = 0.014). Furthermore, higher serum CTHRC1 levels were recorded in seropositive versus seronegative patients (U = 76, P = 0.022) and in RA patients with severe disease activity compared to those with lower disease activity (H = 9.79, P = 0.007). Furthermore, serum CTHRC1 levels were lower in RA patients receiving biological therapy compared to those receiving conventional therapy; however, this difference did not reach statistical significance.
Significant positive correlations were found between CTHRC1 and disease activity, acute-phase reactants, serological markers, functional assessment, fatigue, and erosions detected by ultrasound, while a significant negative correlation was recorded between CTHRC1 and duration of biologic intake (rs =  − 0.45, P = 0.036). Furthermore, on multivariate linear regression analysis, serum CTHRC1 was the only significant predictor for higher disease activity (P = 0.028, B = 0.009, 95% CI 0.001 to 0.017).

Conclusion
RA patients showed higher CTHRC1 serum levels compared to healthy controls, especially those with seropositivity and highly active disease. Furthermore, it was positively associated with poor patient functional outcome, fatigability, and erosive findings by ultrasound, thus suggesting that serum CTHRC1 can be a good predictor for high RA disease activity and possibly severity. Moreover, biological therapy could influence serum CTHRC1 levels in these patients.