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AB0794 Protein degradation markers are associated with clinical features of vasculopathy in systemic sclerosis
  1. D. Khanna1,
  2. K. Au2,
  3. P. Maranian3,
  4. M.K. Karsdal4,
  5. D.J. Leeming5
  1. 1University of Michigan, Ann Arbor
  2. 2Southern California Permanente Medical Group
  3. 3Biostatistics, UCLA, Los Angeles, United States
  4. 4Nordic Bioscience
  5. 5Fibrosis Biology and Biomarkers, Nordic Bioscience, Herlev, Denmark

Abstract

Objectives The pathogenesis of systemic sclerosis (SSc) has 3 distinct yet overlapping pathological processes: inflammation, vasculopathy and fibrosis. Small fragments of proteins generated during lung fibrosis are released into circulation and may be assessed as biochemical markers in plasma of patients. This study assessed the association of clinical and radiological markers of vasculopathy and fibrosis vs. markers of protein degradation.

Methods 55 SSc female patients with no history of clinical atherosclerosis were recruited at an academic center and underwent carotid ultrasound to assess the presence of plaque and carotid intima-media thickness (CIMT). The ultrasound was read by a single radiologist. Clinical data included modified Rodnan skin score (MRSS), pulmonary function tests (FVC% and DLCO%), and presence/absence of digital pulp ulcers. We investigated the associations between the presence/absence of carotid plaque, CIMT, clinical examination, and pulmonary tests vs. 4 novel non-invasive biomarkers. The biomarkers evaluated were protein degradation markers; type III collagen (C3M), type VI collagen (C6M), citrullinated vimentin (VICM) and versican (VCM), all degraded by metalloproteinase. EDTA plasma samples were collected from fasting patients at time of carotid ultrasound and stored at -80°C until use. C3M, C6M, VICM and VCM plasma levels were assessed using newly developed and technically robust competitive ELISAs.

Spearman correlations and Student’s t-test are considered significant at P<0.10.

Results The average of patients was 48 years, disease duaration of 7 years, 51% had limited SSc, and 39% of patients had presence of carotid plaque. Significant associations were noted between features of vasculopathy:1. presence of plaque vs. C6M and VICM (p<0.10), and 2. presence of digital ulcers vs. C3M, C6M and VICM (p<0.10). CIMT score was associated with VCM (coefficient=0.36, p=0.06). Interestingly, no significant association was seen between clinical features of fibrosis (MRSS and PFTs) vs. protein degradation markers (p>0.10 for all analysis).

Conclusions Protein degradation markers are associated with clinical features of vasculopathy. Prospective studies to evaluate the role of these biomarkers in SSc are needed.

Disclosure of Interest D. Khanna Grant/Research support from: NIH, K. Au: None Declared, P. Maranian: None Declared, M. K. Karsdal Employee of: Nordic Bioscience, D. Leeming Employee of: Nordic Bioscience

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