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OP0096 Interferon signature in systemic sclerosis lung microvascular endothelial cells
  1. FA Mendoza1,
  2. S Piera-Velazquez2,
  3. P Wermuth2,
  4. S Addya3,
  5. C Feghali-Bostwick4,
  6. SA Jimenez2
  1. 1Division of Rheumatology and Scleroderma Center
  2. 2Jefferson Institute of Molecular Medicine and Scleroderma Center
  3. 3Kimmel Cancer Center, Thomas Jefferson University, Philadelphia
  4. 4Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, United States


Background Systemic Sclerosis (SSc) is characterized by severe fibroproliferative vasculopathy, exaggerated deposition of extracellular matrix molecules (ECM) in skin and multiple internal organs, and alterations of humoral, cellular and innate immunity. Vascular changes are responsible for the earliest and most severe SSc clinical manifestations, however, the mechanisms responsible have not been elucidated.

Objectives The goal of this study was to analyze the gene expression differences between normal and SSc lung microvascular endothelial cells (EC) to improve the understanding of SSc vasculopathy pathophysiology.

Methods Pulmonary microvascular EC were isolated employing immunomagnetic procedures from lungs from patients with SSc undergoing lung transplantation. Control pulmonary microvascular EC were isolated from autopsies of individuals who died from non-pulmonary causes. Following isolation, microarrays were performed in EC from each group. Expression of genes with the highest differential expression was validated with RT-PCR and Western blots.

Results Interferon-stimulated genes (ISGs) including IFI44L, IFI44, IFI6, IFIH1, IFIT1 displayed the highest differential expression; being overexpressed in EC obtained from the three SSc donors (Figure 1). Other genes such as those encoding ECM production related proteins, genes associated with post-translational methylation, and genes for numerous chemokines and cytokines were also differentially overexpressed in SSc EC. Increased gene expression and increased protein levels of selected ISGs were confirmed by Western blots.

Figure 1.

A: Volcano Plot showing differentially expressed transcripts with 2 fold or greater difference (p<0.05) in expression between SSc and normal control microvascular ECs (130 transcripts corresponding to119 genes). Selected ISGs are encircled (IFI-6, IFIT1, IFI-44,IFI44L,IFIT-3, OAS-1) B: Detail of the resulting heat map of a dendrogram (hierarchically clustered) reveals groups of genes with high expression levels (red squares), low expression levels (blue squares) or background expression levels (yellow squares). Interferon related genes are marked with a red star.

Conclusions Numerous ISGs are differentially overexpressed in SSc pulmonary microvascular EC in comparison with normal control EC. These results suggest that events leading to an interferon response in these cells may play a role in the pathogenesis of SSc lung vasculopathy.


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  3. Matucci-Cerinic M, Kahaleh B, Wigley FM. Review: evidence that systemic sclerosis is a vascular disease. Arthritis and rheumatism 2013; 65(8):1953–62.

  4. Pattanaik D, Brown M, Postlethwaite BC, Postlethwaite AE. Pathogenesis of Systemic Sclerosis. Frontiers in immunology 2015; 6:272.


Disclosure of Interest None declared

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