Abstract
BackgroundDermatomyositis (DM) is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood.Methodology and FindingsWe analyzed genome-wide expression data in DM skin and compared them to those from healthy controls. We observed a robust upregulation of interferon (IFN)-inducible genes in DM skin, as well as several other gene modules pertaining to inflammation, complement activation, and epidermal activation and differentiation. The interferon (IFN)-inducible genes within the DM signature were present not only in DM and lupus, but also cutaneous herpes simplex-2 infection and to a lesser degree, psoriasis. This IFN signature was absent or weakly present in atopic dermatitis, allergic contact dermatitis, acne vulgaris, systemic sclerosis, and localized scleroderma/morphea. We observed that the IFN signature in DM skin appears to be more closely related to type I than type II IFN based on in vitro IFN stimulation expression signatures. However, quantitation of IFN mRNAs in DM skin shows that the majority of known type I IFNs, as well as IFN g, are overexpressed in DM skin. In addition, both IFN-beta and IFN-gamma (but not other type I IFN) transcript levels were highly correlated with the degree of the in vivo IFN transcriptional response in DM skin.Conclusions and SignificanceAs in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, although it is difficult to conclusively define this response as type I or type II. Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue.
Highlights
Dermatomyositis (DM) is a chronic inflammatory disorder that can affect the skin, muscle, and other organs and is associated with significant morbidity and mortality
As in the blood and muscle, DM skin is characterized by an overwhelming presence of an IFN signature, it is difficult to conclusively define this response as type I or type II
Understanding the significance of the IFN signature in this wide array of inflammatory diseases will be furthered by identification of the nature of the cells that both produce and respond to IFN, as well as which IFN subtype is biologically active in each diseased tissue
Summary
Dermatomyositis (DM) is a chronic inflammatory disorder that can affect the skin, muscle, and other organs and is associated with significant morbidity and mortality. DM is considered an autoimmune disease, as it is associated with specific autoantibodies, and its prevalence is associated with particular HLA alleles [2]. Inflamed muscle shows infiltration with B lymphocytes, T lymphocytes, and dendritic cells, and the contribution of each to the disease is not well understood [4,5]. DM muscle expresses large amounts of type I interferon (IFN)-inducible genes [7]. An IFN signature that correlates with overall disease activity is observed in peripheral blood of most DM patients, including patients with juvenile DM [8,9,10]. Dermatomyositis (DM) is an autoimmune disease that mainly affects the skin, muscle, and lung. The pathogenesis of skin inflammation in DM is not well understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
