MDA5+ Dermatomyositis Is Associated with Stronger Skin Type I Interferon Transcriptomic Signature with Upregulation of IFN-κ Transcript

Cassius, C.; Amode, R.; Delord, Marc; Battistella, Maxime; Poirot, Justine; How‐Kit, Alexandre; Lepelletier, C.; Jachiet, Marie; Masson, Adèle de; Frumholtz, L.; Cordoliani, F.; Boccara, David; Lehmann-Che, Jacqueline; Wong, Jennifer; Dubanchet, Sylvie; Alberdi, A.; Mérandet, Marine; Bagot, Martine; Bensussan, Armand; Bouaziz, Jean‐David; Buanec, Hélène Le

doi:10.1016/j.jid.2019.10.020

Cited by 38 publications

(23 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A common pathophysiological model has therefore been proposed, based on the secretion of keratinocyte-derived CXCL10 following skin exposure to IFN-I ( 125 – 128 ). Consistent with this observation, the expression of CXCL10 as well as the expression of IFN-I induced proteins (ISG15, MxA) are upregulated in the skin of anti-MDA5 Abs positive patients ( 108 , 109 , 126 , 129 ). Endothelial cells stimulated by IFN-I could also constitute another source of CXCL10 ( 130 ).…”

Section: Pathogenesis Of the Diseasesupporting

confidence: 71%

“…Whether we consider skin or lung lesions, IFN-I seems to be the starting point for all the pathophysiological pathways described above. Indeed, IFN-I signaling is enhanced in anti-MDA5 DM, in skin and in serum, more than in other DM, suggesting the presence of a specific trigger of the IFN-I pathway in the disease ( 109 , 129 , 136 ). Here we assume that anti-MDA5 Abs could be the cornerstone of the dysregulation of the IFN-I pathway in anti-MDA5 DM.…”

Section: Pathogenesis Of the Diseasementioning

confidence: 99%

See 1 more Smart Citation

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

2021

View full text Add to dashboard Cite

Anti-MDA5 dermatomyositis is a rare systemic autoimmune disease, historically described in Japanese patients with clinically amyopathic dermatomyositis and life-threatening rapidly progressive interstitial lung disease. Subsequently, the complete clinical spectrum of the disease was enriched by skin, articular and vascular manifestations. Depending on the predominance of these symptoms, three distinct clinical phenotypes with different prognosis are now defined. To date, the only known molecular component shared by the three entities are specific antibodies targeting MDA5, a cytosolic protein essential for antiviral host immune responses. Several biological tools have emerged to detect these antibodies, with drawbacks and limitations for each of them. However, the identification of this highly specific serological marker of the disease raises the question of its role in the pathogenesis. Although current knowledge on the pathogenic mechanisms that take place in the disease are still in their enfancy, several lines of evidence support a central role of interferon-mediated vasculopathy in the development of skin and lung lesions, as well as a possible pathogenic involvement of anti-MDA5 antibodies. Here, we review the clinical and biological evidences in favor of these hypothesis, and we discuss the contribution of emerging therapies that shed some light on the pathogenesis of the disease.

show abstract

Section: Pathogenesis Of the Diseasesupporting

confidence: 71%

Section: Pathogenesis Of the Diseasementioning

confidence: 99%

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

2021

View full text Add to dashboard Cite

show abstract

“…Histopathological features of the inverse Gottron's papules showed hyperkeratosis of the corneal layers, liquefaction degeneration of the basal layers, and individual cell keratinization in the epidermis in all cases, which were comparable to those of Gottron's papules. MDA5 positivity in dermatomyositis is associated with type I interferon (IFN) activity 7 and vasculopathy 8 ; however, vasculopathy was not observed in our cases. Enhanced expression of IFN‐inducible proteins such as STAT1, ISG15, and MxA was recently reported 9 .…”

Section: Figurecontrasting

confidence: 56%

Inverse Gottron's papules in patients with dermatomyositis: an underrecognized but important sign for interstitial lung disease

et al. 2020

View full text Add to dashboard Cite

region. Nonetheless, a considerable percentage of positive tests revealed a dermatophyte infection. In our clinical practice, tinea corporis is not one of the most common trunk dermatoses, but it should be kept in mind that old age, along with an immunocompromised status, represents a predisposing factor. 2 Our results provide for a real-life perspective in a particular poorly studied age group, the elderly patients. Our study, in line with literature and demographic data, allows us to have a match with the routine daily practice and makes us remember the fundamental clinical aspects with an everyday increasing aging population.

show abstract

“…Distal TGF-b and p63-responsive enhancers and MAPK signaling cascades appear to be necessary for IFNj regulation (90,91). Elevated IFNj expression has been associated with various skin manifestations of autoimmune disorders, such as dermatomyositis (92), systemic and cutaneous lupus erythematosus (93), and psoriasis (94). IFN-k could promote inflammatory responses observed in patients by inducing ISG expression (95) and promoting secretion of the proinflammatory cytokine, IL-6.…”

Section: Tissue and Species-specific Ifn Responsesmentioning

confidence: 99%

Beyond Good and Evil: Molecular Mechanisms of Type I and III IFN Functions

Dowling

Forero

2022

The Journal of Immunology

View full text Add to dashboard Cite

IFNs are comprised of three families of cytokines that confer protection against pathogen infection and uncontrolled cellular proliferation. The broad role IFNs play in innate and adaptive immune regulation has placed them under heavy scrutiny to position them as “friend” or “foe” across pathologies. Genetic lesions in genes involving IFN synthesis and signaling underscore the disparate outcomes of aberrant IFN signaling. Abrogation of the response leads to susceptibility to microbial infections whereas unabated IFN induction underlies a variety of inflammatory diseases and tumor immune evasion. Type I and III IFNs have overlapping roles in antiviral protection, yet the mechanisms by which they are induced and promote the expression of IFN-stimulated genes and inflammation can distinguish their biological functions. In this review, we examine the molecular factors that shape the shared and distinct roles of type I and III IFNs in immunity.

show abstract

MDA5+ Dermatomyositis Is Associated with Stronger Skin Type I Interferon Transcriptomic Signature with Upregulation of IFN-κ Transcript

Cited by 38 publications

References 15 publications

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

Inverse Gottron's papules in patients with dermatomyositis: an underrecognized but important sign for interstitial lung disease

Beyond Good and Evil: Molecular Mechanisms of Type I and III IFN Functions

Contact Info

Product

Resources

About