Capturing the heterogeneity in systemic sclerosis with genome-wide expression profiling

Abstract

Heterogeneity in the clinical presentation and basic science findings of systemic sclerosis (SSc) has hindered the understanding of pathogenesis and development of effective treatments. Genome-wide profiling of SSc has measured this heterogeneity. Gene expression studies of diffuse SSc skin have shown reproducible, disease-specific gene expression signatures when compared with healthy controls and, surprisingly, disease-specific gene expression was found in both lesional and non-lesional skin. SSc-specific gene expression in peripheral blood cells and the lungs has also been demonstrated. Hypothesis-driven approaches that assess the contribution of individual pathways provide insight into the etiology of gene expression subsets.

Keywords::

• animal models
• gene expression profiling
• intrinsic subsets
• scleroderma
• signaling
• systemic sclerosis
• TGF-β

Financial & competing interests disclosure

Michael L Whitfield and Jennifer L Sargent were supported by a grant from the Scleroderma Research Foundation. Michael L Whitfield received additional support from an Arthritis Investigator Award from the Arthritis Foundation, and from NIH grant U01AR055063. Michael L Whitfield and Jennifer L Sargent have filed patent applications for gene expression biomarkers in scleroderma. Michael L Whitfield is a scientific founder and holds an interest in Celdara Medical, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.