FRI0326 SEROLOGICAL ASSESSMENT OF THE FIBROTIC INDEX IN SCLEROSIS: A CROSS SECTIONAL STUDY
Authors: Pernille Juhl, Anne-Christine Bay-Jensen, Roger Hesselstrand, Anne Sofie Siebuhr, Dirk Wuttge
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> The hallmark of systemic sclerosis (SSc) is fibrosis of the skin. The interstitial matrix is rich in type I and III collagen while type IV collagen is the main collagen of the basement membrane. These two types of matrix are anchored together by other matrix proteins such as type VI collagen. Tissue turnover is in a delicate equilibrium of tissue formation and degradation, which may be altered in pathologies such as SSc, in which there is a net increase in tissue. By using advanced serological biomarkers tissue turnover, tissue formation and tissue degradation may be assed separately, to quantify the tissue balance. The hypothesis of the current study was that the tissue balance was altered in SSc as compared to healthy, and that limited and diffuse SSc would present with different turnover rates. <h3>Objectives</h3> The objective was to quantify the tissue turnover balance in a cross-sectional study in limited and diffuse SSc. <h3>Methods</h3> Forty-three patients fulfilling the 2013 ACR/EULAR criteria for SSc were included. The study included limited (lcSSc, n= 20) and diffuse SSc (dcSSc, n=23) (recruited at Lund University, approval number Dnr 590/2008). Ten healthy controls were included. Biomarkers of type III, IV and VI collagen formation (PRO-C3, PRO-C4, PRO-C6) and degradation (C3M, C4M, C6M) were measured cross sectional in serum samples by competitive ELISAs. The fibrotic index of collagens (FICol) were examine (formation/degradation). Difference between groups were tested by Mann-Whitney U test and correlations by Spearman's correlation. <h3>Results</h3> There was no significant difference in gender, age or BMI between lcSSc and dSSc. The mean age of the population was 53.5 years and 79% were female. LcSSc had a longer disease duration (lcSSc: 32.3 month (SD: 41.0), dcSSc: 13.5 month (SD 14.9), P=0.05) and a lower modified Rodnan skin score (mRSS, lcSSc: 4.25 points (SD: 3.1), dcSSc: 20.3 points (11.7), P&lt;0.0001) compared to dcSSc as expected. Type III and VI collagen formation were both significantly increased in dcSSc compared to lcSSc (PRO-C3: 18.6 ng/ml (SD: 10.0) vs 13.0 ng/ml (SD: 6.5) (P=0.01), PRO-C6: 16.7 ng/ml (SD: 6.6) vs 12.1 ng/ml (SD: 4.9) (P=0.01), Figure 1). Type III collagen degradation were decreased in dcSSc compared to lcSSc (C3M: 13.3 ng/ml (SD: 2.9) vs 17.4 ng/ml (SD: 7.5) (P=0.03)). Neither type IV collagen formation nor type III, IV or VI collagen degradation were significantly different. The fibrotic index of type III and VI collagen (FICol3 and FICol6) were significantly increased in dcSSc compared to lcSSc (FICol3: 1.4 (SD: 0.6) vs 0.8 (SD: 0.3) (P=0.0001), FICol6: 1.2 (SD: 0.5) vs 0.9 (SD: 0.3) (P=0.03), Figure 2). The fibrotic index of type IV collagen (FICol4) were not different between the two groups but were both 1.5 times higher than the levels of healthy (healthy: 6.9, lcSSc 10.4 (SD: 3.3), dcSSc: 10.5 (SD:3,1)). Both type III and VI collagen formation correlated moderately with mRSS with rho's of 0.53 (P=0.0003) and 0.4 (p=0.008), respectively. FICol3 correlated with a rho of 0.59 (P&lt;0.0001) and FICol6with a rho of 0.35 (P=0.04). <h3>Conclusion</h3> The tissue turnover balance was clearly altered in both limited and diffuse SSc as compared to healthy controls. In addition, diffuse SSc presented with a more screwed balance in the fibrotic index towards tissue formation and disease progression. This study shows the importance of looking at both collagen formation and degradation. The collagen tissue turnover could be beneficial in following patients' fibrosis development and possibly identifying if they are progressing or in remission. <h3>Disclosure of Interests</h3> Pernille Juhl: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Roger Hesselstrand: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Dirk Wuttge: None declared