Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic sclerosis (SSc) is a complex autoimmune disease with extensive fibrosis of the skin and internal organs in which extracellular matrix (ECM) remodeling is a key pathogenic process. Given the clinical heterogeneity and the individual disease course of SSc, biomarkers to allow personalized medicine are highly needed. We evaluated the potential of selected ECM neoepitopes as serological biomarkers for diagnosis, prognostic of progression and prediction of clinical outcomes.
Methods: Stable SSc patients (n=151), SSc progressors (n=21, either 10% decrease in FVC% predicted or increase in mRSS ≥25% and 5 points on 1 year clinical follow up) meeting the ACR/EULAR classification criteria and healthy controls (HC; n=29) were analyzed. Longitudinal clinical assessment, data recording and sera collection were done according to EUSTAR standards. ECM-degradation (C3M, C4M2, BGM, VICM) and ECM-formation biomarkers (P1NP, Pro-C3, Pro-C6) were measured in serum using ELISA-based assays. Differences in biomarker levels were analyzed with respect to several fibrosis-related clinical outcomes as well as the Valentini disease activity score (VDAS). Statistical analysis was performed by Man-Whitney U, Kruskal-Wallis and Spearman tests, as well as multivariate logistic regression, adjusted for sex and age. Biomarkers’ sensitivity and specificity was examined by ROC analysis.
Results: The expression of C4M2, Pro-C3, BGM and C3M was significantly increased in SSc patients compared to HC (p<0.0001, AUC=0.93; p<0.0001, AUC=0.74; p=0.003, AUC=0.67; p<0.0001; AUC=0.93, respectively). Furthermore, Pro-C3, VICM and Pro-C6 levels were significantly higher in SSc progressors vs. HC (p<0.0001, AUC=0.85; p=0.003, AUC=0.75; p=0.0002, AUC=0.81, respectively), whereas P1NP was significantly lower (p=0.04, AUC=0.67). Interestingly, ECM-degradation markers C4M2, BGM and C3M were significantly lower in SSc progressors vs. SSc patients (p<0.0001; p<0.005; p<0.0001, respectively), whereas the formation marker Pro-C3 was slightly higher, but without reaching statistical significance (Figure 1). Pro-C3 was significantly higher in patients with DLCO SB <70% (p=0.03), moderate-severe dyspnea (p=0.02) and active disease (VDAS ≥3, p=0.02) and showed a mild correlation to the VDAS (r= -0.29; p=0.000).
Conclusion: These data indicate that ECM neoepitopes could not only differentiate between HC and SSc patients but, even more, could help identify patients prone to progress at 1 year clinical follow up. The significant decrease in ECM-degradation markers in SSc progressors compared to stable patients suggests an impairment of collagen degradation in this group. ECM neoepitopes arise as potential new biomarkers in SSc. Figure 1.
To cite this abstract in AMA style:Dobrota R, Jordan S, Juhl P, Wildi L, Maurer B, Bay-Jensen AC, Karsdal MA, Siebuhr AS, Distler O. Collagen Formation/Degradation Neoepitopes Are Promising Biomarkers for Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/collagen-formationdegradation-neoepitopes-are-promising-biomarkers-for-systemic-sclerosis/. Accessed October 20, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/collagen-formationdegradation-neoepitopes-are-promising-biomarkers-for-systemic-sclerosis/