Anti- Melanoma Differentiation-Associated Gene 5 Antibody Positive Dermatomyositis: Recent Progress in Pathophysiology and Treatment

Abstract

Purpose of review: Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a rare systemic autoimmune disease characterized by a clinically amyopathic presentation and a high-risk association with rapidly progressive interstitial lung disease. Although frequently fatal, the underlying mechanisms remain incompletely understood. This review provides a comprehensive summary of recent advances in research on MDA5-DM, aiming to deepen our understanding of its pathogenic mechanisms and to accelerate future basic research that will contribute to the development of novel therapeutic strategies.

Recent findings: Recent advancements have shed light on various aspects of this disease, including genetic and environmental factors contributing to disease susceptibility and the immunopathological processes and cytokine networks. Furthermore, significant progress has been made in understanding the pathogenicity, epitope recognition, and production mechanisms of anti-MDA5 antibodies, which have long been subjects of debate. On the therapeutic front, in addition to the conventional triple-combination regimen, emerging efficacy of JAK inhibitors and rituximab has been recognized. The development of biologics targeting lymphocytes offers additional hope for advancing therapeutic options. Advancing our understanding of the latest pathophysiological mechanisms of MDA5-DM is expected to pave the way for the development of safer and more effective therapeutic strategies.

Keywords: Anti- Melanoma differentiation-associated gene 5 antibody positive dermatomyositis; MDA5; Mechanism; Pathogenesis.

Fig. 1

Genetic and environmental factors associated with MDA5-DM. DC: dendritic cell, IFN: interferon, MDA5: melanoma differentiation-associated gene 5, TLR: toll like receptor. This figure was originally created by the author using Microsoft PowerPoint (Office 2019)

Fig. 2

Presumed pathogenesis of anti-MDA5 antibodies. LDG: low-density granulocytes, pDC: plasmacytoid dendritic cells. This figure was originally created by the author using Microsoft PowerPoint (Office 2019)

Fig. 3

Association between clinical phenotypes and recognition epitopes of anti-MDA5 antibodies. CTD: C-terminal domain, ILD: interstitial lung disease. This figure was originally created by the author using Microsoft PowerPoint (Office 2019)

Fig. 4

Treatment choice of MDA5-DM. IVIG: Intravenous Immunoglobulin. This figure was originally created by the author using Microsoft PowerPoint (Office 2019)