Dermatomyositis

Krathen, Michael; Fiorentino, David; Werth, V.

doi:10.1159/000131751

Cited by 46 publications

(36 citation statements)

References 75 publications

(186 reference statements)

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“…Similarities to muscle disease exist in the skin: first, vasculopathy and vascular deposition of complement components can be detected in cutaneous DM skin [13], [14]; second, there is damage to the parenchymal cells (e.g. keratinocytes) [11]; third, DM skin appears to be characterized by increased abundance of several gene products that are known to be upregulated by IFN [15], [16] as well as by increased numbers of plasmacytoid dendritic cells [17], [18]. It has been proposed that some of these gene products, such as CXCL9/10/11, act as chemoattractrants for CXCR3-bearing T lymphocytes which can then perpetuate inflammation and keratinocyte necrosis [16].…”

Section: Introductionmentioning

confidence: 95%

Interferon and Biologic Signatures in Dermatomyositis Skin: Specificity and Heterogeneity across Diseases

et al. 2012

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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.

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Section: Introductionmentioning

confidence: 95%

Interferon and Biologic Signatures in Dermatomyositis Skin: Specificity and Heterogeneity across Diseases

et al. 2012

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“…Histologically, dermatomyositis skin lesions are characterized by apoptosis/necrosis of keratinocytes, perivascular inflammation, increased dermal mucin deposition and endothelial cell deposition [26]. Active skin lesions from dermatomyositis patients were compared with controls and a dermatomyositis signature was identified.…”

Section: Review Of Recently Published Follow-up Studiesmentioning

confidence: 99%

What does global gene expression profiling tell us about the pathogenesis of systemic sclerosis?

Assassi

Mayes

2013

Current Opinion in Rheumatology

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Purpose of review The purpose of this study is to review recent hypothesis-driven studies that utilize global gene expression data for elucidating the molecular basis of systemic sclerosis (SSc) and its various clinical manifestations. Recent findings The longitudinal skin gene expression studies indicate that the previously identified molecular subsets are stable over time and might identify inherent subgroups of SSc patients. Skin transcript follow-up studies indicate that the Wnt/β-catenin pathway plays an important role in promotion of fibrogenesis in fibroblasts and preadipocytes. Furthermore, the transcript profile of sclerodermatous graft-versus-host disease (sclGVHD) mice resembles the skin transcriptomes of a subgroup of SSc patients with IL13/IL4-inducible skin signature wherein the profibrotic chemokine CCL2 plays a key role. The comparison of skin biopsies from SSc patients to skin lesions of patients with cutaneous lupus and dermatomyositis has provided valuable information about the interferon (IFN) signature in these autoimmune diseases. Furthermore, plasma IFN-inducible chemokines correlate with the IFN gene expression score in SSc patients, enabling researchers to examine this molecular signature in large SSc cohorts with serum or plasma collection. Summary Global gene expression profiling in skin and peripheral blood can contribute to a better understanding of SSc pathogenesis and identify novel biomarkers and therapeutic targets.

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“…Although it may be humorally mediated, cell-mediated autoimmunity may be a preferred mechanism, and dysfunction of the immune system may also play an important role in the pathogenesis [93]. In a case of dermatomyositis associated with SCLC, researchers observed a marked increase in the number of circulating natural killer cells (CD3 À CD16 þ ) with a homogeneous phenotype (CD56 À CD94 À CD159a À CD244 þ ) [94].…”

Section: Dermatomyositismentioning

confidence: 99%