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SAT0214 Macrophage Activation and Biglycan as Disease Activity and Diagnostic Biomarkers in Systemic Sclerosis
  1. A.S. Siebuhr1,
  2. R.T. Domsic2,
  3. P. Juhl1,
  4. A.-C. Bay-Jensen1,
  5. M.A. Karsdal1,
  6. N. Franchimont3,
  7. J. Chavez3
  1. 1Biomarkers and Research, Nordic Bioscience, Herlev, Denmark
  2. 2Scleroderma Center, University of Pittsburgh, Pittsburgh
  3. 3Clinical Development, Biogen, Cambridge, United States

Abstract

Background Systemic sclerosis (SSc) is a chronic disease characterized by vascular damage, immunologic activation and excessive extracellular matrix (ECM) deposition in the skin and internal organs. The excessive ECM deposition leads to the release of ECM fragments into circulation, where they may be quantified as biomarkers. Activation of macrophages is a hallmark of the immunologic activation in autoimmune diseases and the activation lead to uncontrolled ECM destruction. In addition, activated macrophages has been shown to secrete the intermediate filament vimentin, making it an ideal protein biomarker of activated macrophages.

Objectives The objectives were to investigate 1) if biomarkers of ECM turnover and macrophage activation could seperate diffuse SSc patients and healthy and 2) the diagnostic power of these biomarkers.

Methods Diffuse SSc patients (n=40) fulfilling the American College of Rheumatology criteria were included. Patients were divided into early and late diffuse based on disease duration (n=20 per group). Furthermore, early SSc patients were divided into intermediate and rapid skin thickness progression rate (STPR; n=10 in each). Twenty healthy controls were included. The macrophage activation biomarker citrullinated and MMP-degraded vimentin (VICM), the ECM biomarkers matrix metalloproteinase (MMP) degraded biglycan (BGM) and MMP-7 degraded elastin (ELM-7) were assessed in serum. The currently best diagnostic and prognostic biomarker (platelet factor 4; CXCL4) was furthermore investigated in serum. Statistical differences between the groups were tested by Kruskal-Wallis test with Dunn's multiple comparisons test. Diagnostic capacity was analysed by receiver operating characteristics (ROC) area under the curve (AUC) on healthy vs. diseased, healthy vs. early or late diffuse and between early and late diffuse.

Results VICM level was significantly increased in early SSc compared to late SSc (p=0.023). The VICM level in the rapid STPR was significantly increased compared to healthy (p=0.025) and intermediate STPR (p=0.022). Of notice, the VICM level of intermediate STPR was at the level of healthy. BGM level was significantly increased in early diffuse SSc compared to healthy (p=0.0003). Both early SSc groups (rapid and intermediate STPR) was increased compared to healthy (p=0.012 and p=0.0022, respectively). There were no difference in the ELM-7 and CXCL4 levels between any groups.

The diagnostic capacity of the biomarkers were assessed. VICM did not reach significance, but reached an AUC of 0.71 for diagnosing early vs. late SSc. BGM had an AUC of 0.79 for healthy vs. SSc. The diagnostic power increased when only testing early SSc (AUC=0.84) and decreased when only testing late SSc (AUC=0.74).

Conclusions VICM could identify the group with rapid STPR, whereas BGM was a possible diagnostic biomarker of early SSc. CXCL4 was in this study not a diagnostic tool of SSc as previously shownA. The current study illustrates that serological biomarkers of BGM could be a diagnostic tools in SSc and that macrophage activation (VICM) could be potential biomarkers of SSc disease activity (VICM).

Disclosure of Interest A. S. Siebuhr Employee of: NORDIC BIOSCIENCE A/S, R. Domsic: None declared, P. Juhl Employee of: NORDIC BIOSCIENCE A/S, A.-C. Bay-Jensen Employee of: NORDIC BIOSCIENCE A/S, M. Karsdal Shareholder of: NORDIC BIOSCIENCE A/S, Employee of: NORDIC BIOSCIENCE A/S, N. Franchimont: None declared, J. Chavez: None declared

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