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- W4254629276 abstract "Dermatomyositis (DM) is a chronic auto-immune disorder affecting skin and muscle. The transcriptomic signature of DM is characterized by a type I interferon (IFN) signature which has been shown to correlate with disease activity. Among autoantibodies, anti-Melanoma differentiation-associated gene 5 (MDA5) antibodies are associated with a unique presentation. Herein, we assessed the global gene expression in the skin of 3 MDA5+ DM and compared it to 5 MDA5- DM and 5 healthy individuals. The principal component analysis clustered independently according to the serology, indicating distinct molecular profiles. Among the most highly upregulated genes in MDA5+ skin were IFIT2, CXCL10 and IFIH1; the type I IFN pathway was also significantly upregulated. To confirm the type I interferon signature in MDA5+ DM, we showed using MxA immunohistochemistry that MDA5+ DM skin samples expressed more MxA in inflammatory infiltrate than MDA5- skin samples. Finally, to decipher the origin of the type I IFN signature in DM skin, we focused on the type of interferons. Interestingly, IFN-κ gene was the only interferon significantly elevated in MDA5+ skin (FC=2.27; q=0.03) compared to healthy skin. In MDA5- compared to healthy skin, IFN-κ was elevated but not significantly (FC=1.9; q=0.25). We confirm here that DM skin involvement is associated with a specific transcriptomic signature comprising an activation and infiltration of immune cells and a type I IFN response signature. The type I IFN signature is more strongly expressed in the skin of MDA5+ versus MDA5- DMs. Our data support the potential role of keratinocytes and IFN-κ over IFN-α in the skin pathophysiology of MDA5+ DM." @default.
- W4254629276 created "2022-05-12" @default.
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- W4254629276 date "2019-09-01" @default.
- W4254629276 modified "2023-09-30" @default.
- W4254629276 title "042 MDA5+ dermatomyositis is associated with stronger skin type I interferon transcriptomic signature with up-regulation of IFN-κ transcript" @default.
- W4254629276 doi "https://doi.org/10.1016/j.jid.2019.07.045" @default.
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