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Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System

Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5(+) DM) is typically characterized by cutaneous manifestations, amyopathic or hypomyopathic muscle involvement, and a high incidence of rapid progressive interstitial lung disease (RP-ILD). However, the exact etio...

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Autores principales: Hu, Huifang, Yang, Hang, Liu, Yi, Yan, Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818857/
https://www.ncbi.nlm.nih.gov/pubmed/35141258
http://dx.doi.org/10.3389/fmed.2021.833114
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author Hu, Huifang
Yang, Hang
Liu, Yi
Yan, Bing
author_facet Hu, Huifang
Yang, Hang
Liu, Yi
Yan, Bing
author_sort Hu, Huifang
collection PubMed
description Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5(+) DM) is typically characterized by cutaneous manifestations, amyopathic or hypomyopathic muscle involvement, and a high incidence of rapid progressive interstitial lung disease (RP-ILD). However, the exact etiology and pathogenesis of this condition has yet to be fully elucidated. Melanoma differentiation-associated gene 5 (MDA5), as the autoantigen target, is a member of the retinoic acid-inducible gene-I (RIG-I) family. The MDA5 protein can function as a cytosolic sensor that recognizes viral double-strand RNA and then triggers the transcription of genes encoding type I interferon (IFN). Therefore, it was presumed that viruses might trigger the overproduction of type I IFN, thus contributing to the development of MDA5(+) DM. Emerging evidence provides further support to this hypothesis: the increased serum IFNα level was detected in the patients with MDA5(+) DM, and the type I IFN gene signature was upregulated in both the peripheral blood mononuclear cells (PBMCs) and the skin tissues from these patients. In particular, RNA sequencing revealed the over-expression of the type I IFN genes in blood vessels from MDA5(+) DM patients. In addition, Janus kinase (JAK) inhibitors achieved the promising therapeutic effects in cases with interstitial lung disease (ILD) associated with MDA5(+) DM. In this review, we discuss the role of the type I IFN system in the pathogenesis of MDA5(+) DM.
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spelling pubmed-88188572022-02-08 Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System Hu, Huifang Yang, Hang Liu, Yi Yan, Bing Front Med (Lausanne) Medicine Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (MDA5(+) DM) is typically characterized by cutaneous manifestations, amyopathic or hypomyopathic muscle involvement, and a high incidence of rapid progressive interstitial lung disease (RP-ILD). However, the exact etiology and pathogenesis of this condition has yet to be fully elucidated. Melanoma differentiation-associated gene 5 (MDA5), as the autoantigen target, is a member of the retinoic acid-inducible gene-I (RIG-I) family. The MDA5 protein can function as a cytosolic sensor that recognizes viral double-strand RNA and then triggers the transcription of genes encoding type I interferon (IFN). Therefore, it was presumed that viruses might trigger the overproduction of type I IFN, thus contributing to the development of MDA5(+) DM. Emerging evidence provides further support to this hypothesis: the increased serum IFNα level was detected in the patients with MDA5(+) DM, and the type I IFN gene signature was upregulated in both the peripheral blood mononuclear cells (PBMCs) and the skin tissues from these patients. In particular, RNA sequencing revealed the over-expression of the type I IFN genes in blood vessels from MDA5(+) DM patients. In addition, Janus kinase (JAK) inhibitors achieved the promising therapeutic effects in cases with interstitial lung disease (ILD) associated with MDA5(+) DM. In this review, we discuss the role of the type I IFN system in the pathogenesis of MDA5(+) DM. Frontiers Media S.A. 2022-01-24 /pmc/articles/PMC8818857/ /pubmed/35141258 http://dx.doi.org/10.3389/fmed.2021.833114 Text en Copyright © 2022 Hu, Yang, Liu and Yan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Hu, Huifang
Yang, Hang
Liu, Yi
Yan, Bing
Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System
title Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System
title_full Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System
title_fullStr Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System
title_full_unstemmed Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System
title_short Pathogenesis of Anti-melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis: A Concise Review With an Emphasis on Type I Interferon System
title_sort pathogenesis of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis: a concise review with an emphasis on type i interferon system
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8818857/
https://www.ncbi.nlm.nih.gov/pubmed/35141258
http://dx.doi.org/10.3389/fmed.2021.833114
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