Date: Sunday, November 5, 2017
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Altered extracellular matrix (ECM) remodeling leading to fibrosis is a key pathogenic process in systemic sclerosis (SSc). We previously showed that collagen formation and degradation metabolites are deregulated in SSc and that type III collagen turnover could identify progressive patients (1). Here, we report additional longitudinal analysis exploring serological collagen biomarkers potential for diagnosis and prediction of progression of skin and lung fibrosis in SSc.
Patients (n=174) meeting the 2013 ACR/EULAR classification criteria for SSc and age and sex matched healthy controls (HC; n=29) were analyzed. 10% decrease in FVC% predicted or increase in mRSS ≥25% and 5 points at 1 year follow up defined progression. “Stable” were patients not meeting these criteria. Longitudinal clinical assessment and data, and baseline sera collection were conducted by EUSTAR quality standards. Collagen degradation (C3M, C4M2), BGM (MMP-degraded biglycan) and collagen formation markers (P1NP, P4NP7S, PRO-C3, PRO-C5, Pro-C6) were measured in serum by ELISA. Statistical analysis included Mann-Whitney U, Kruskal-Wallis tests, ROC analysis, and binary logistic regression.
174 patients with SSc as well as 29 HC were analysed. There were 25 (14%) SSc patients who progressed during 1 year. Baseline levels of most collagen biomarkers were higher in SSc compared to HC. C3M, C4M2 and PRO-C3 distinguished well between HC and SSc patients: C3M (AUC 0.90, p<0.001, 95%CI 0.85-0.95), C4M2 (AUC 0.90, p<0.001, 95%CI 0.85-0.94), PRO-C3 (AUC 0.75, p<0.001, 95%CI 0.67-0.83) (Figure 1). In addition to the previously reported ratio of PRO-C3/C3M (1), C3M and C4M2 predicted 1-year progression: C3M (AUC 0.87, p<0.001, 95%CI [0.79-0.95]), C4M2 (AUC 0.78, p<0.001, 95%CI [0.68-0.88]). A cut-off for PRO-C3/C3M at >1.2 showed a sensitivity of 84% with a specificity of 78% to predict progressive patients. In logistic regression adjusted for age and sex, PRO-C3M/C3M could predict decrease of FVC≥10% (OR 3.8, 95%CI [1.5-9.2], p=0.004) and increase of mRSS≥25% and 5 points (OR=2.1, 95%CI [1.0-4.2], p=0.04). Further, PRO-C3/C3M (OR 2.87, 95%CI [1.8-4.5], p<0.001) and C3M (OR 0.69, 95%CI [0.6-0.8], p<0.001) were identified as significant predictors of progression of skin and lung fibrosis.
The dysbalance of collagen turnover suggests decreased collagen degradation in progressive vs. stable patients. Markers of collagen III and IV particularly arise hereby as potential new diagnostic and prognostic biomarkers in SSc.
1. New collagen biomarkers predict progression of fibrosis in systemic sclerosis. R. Dobrota, S. Jordan, P. Juhl, B. Maurer, L. Wildi, A.-C. Bay-Jensen, M.A. Karsdal, A.S. Siebuhr, O. Distler. Ann Rheum Dis, vol. 76, suppl. 2, 2017:625.
Figure 1. Levels of biomarkers in healthy controls (HC) and patients with systemic sclerosis (SSc)
To cite this abstract in AMA style:Dobrota R, Jordan S, Juhl P, Maurer B, Wildi L, Bay-Jensen AC, Karsdal M, Siebuhr AS, Distler O. Prediction of Fibrosis Progression in Systemic Sclerosis By Collagen Biomarkers [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/prediction-of-fibrosis-progression-in-systemic-sclerosis-by-collagen-biomarkers/. Accessed August 8, 2020.
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