Overlapping gene expression profiles indicative of antigen processing and the interferon pathway characterize inflammatory fibrotic skin diseases

Abstract

Inflammatory fibrotic disorders have been of high interest both for dermatologists and rheumatologists. Although the phenotypic end stage of this group of diseases is ultimately the same, namely fibrosis, patients present with different clinical features and are often treated with distinct therapeutic modalities. This review addresses whether there is evidence for different underlying molecular pathways in the various inflammatory fibrotic diseases such as localized scleroderma, pediatric lichen sclerosus, adult lichen sclerosus, eosinophilic fasciitis and systemic sclerosis. To investigate this, a large number of gene expression microarray studies performed on skin or fibroblasts from patients with these aforementioned diseases were described, (re-)analysed, and compared. As suspected by the heterogeneous phenotype, most diseases showed unique gene expression features. Intriguingly, a clear overlap was observed between adult and pediatric lichen sclerosus and localized scleroderma, in antigen processing and the interferon pathway. Delineating the cause and consequence of these pathways may generate novel tools to better characterize and more effectively treat these patients.

Keywords::

• eosinophilic fasciitis
• fibrosis
• lichen sclerosus
• localized scleroderma
• skin
• systemic sclerosis

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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

Key issues

• Inflammatory fibrotic disorders including systemic sclerosis (SSc), localized scleroderma (LoS), lichen sclerosus (LiS) and eosinophilic fasciitis are heterogeneous diseases, all ultimately leading to fibrosis of the skin. Up till now, it is not known whether these diseases share a common pathogenic pathway; gene expression studies on skin or fibroblasts of these patients give us the opportunity to investigate the differences and similarities in the pathogenesis.

• Gene expression profiling of lesional and nonlesional SSc skin can divide patients into specific subsets. In general, SSc seems to be characterized by a proinflammatory gene expression profile, and fibroblasts of SSc patients show a genetically predisposed gene expression profile.

• Microarray data of LoS and eosinophilic fasciitis skin are scarce. In LoS, gene expression analysis suggests the presence of an inflammatory response mediated by T cells; the results of two genome-wide expression studies in genital LiS also suggest the involvement of an inflammatory response mediated by T cells.

• Reanalysis of the existent microarray data in SSc, LoS and LiS revealed an overlap between LoS and LiS regarding the interferon- and antigen-processing pathway.

Notes