ArticleRheumatology (Oxford, England)2024
Autoantibodies against the melanoma differentiation-associated protein 5 in patients with dermatomyositis target the helicase domains.
Article in Rheumatology (Oxford, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Dermatomyositis with Anti-MDA5 Autoantibodies After SARS-CoV-2 mRNA Vaccination Treated with Tofacitinib: Integrating Literature Evidence and a Novel Observation.Antibodies (Basel, Switzerland) · 2026Review
- Autoantibody internalization in myositis skeletal muscle: Emerging evidence, mechanistic insights, and therapeutic relevance.Autoimmunity reviews · 2026Review
- Pathogenesis and Treatment of Interstitial Lung Disease Accompanied by Anti-melanoma Differentiation-associated Gene 5-positive Idiopathic Inflammatory Myopathies.Internal medicine (Tokyo, Japan) · 2026Review
- Anti- Melanoma Differentiation-Associated Gene 5 Antibody Positive Dermatomyositis: Recent Progress in Pathophysiology and Treatment.Current rheumatology reports · 2025Review
- When viral infections meet the anti-MDA5 antibody-positive dermatomyositis.Frontiers in immunology · 2025Review
- An update on autoantibodies in the idiopathic inflammatory myopathies.Nature reviews. Rheumatology · 2025Review
- Recent Updates on the Pathogenesis of Inflammatory Myopathies.Current rheumatology reports · 2024Review
- Pathological autoantibody internalisation in myositis.Annals of the rheumatic diseases · 2024Article
- A comprehensive review of dermatomyositis treatments - from rediscovered classics to promising horizons.Expert review of clinical immunology · 2024Review
- Pathogenic autoantibody internalization in myositis.medRxiv : the preprint server for health sciences · 2024Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivesClinical observations in patients with dermatomyositis (DM) and autoantibodies against the melanoma differentiation-associated protein 5 (MDA5) suggest that the autoantibodies contribute to the pathogenesis of MDA5(+) DM. To gain insight into the role of the anti-MDA5 autoantibodies, we aimed to identify their binding sites on the different domains of the MDA5 protein.
methodsWe developed an in-house ELISA to assess the reactivity against the MDA5 domains (conformational epitopes) in plasma (n = 8) and serum (n = 24) samples from MDA5(+) patients with varying clinical manifestations and disease outcomes. The reactivities were also assessed using western blot (linearized epitopes). An ELISA-based depletion assay was developed to assess cross-reactivity among the different MDA5 domains.
resultsAll eight plasma samples consistently showed reactivity towards conformational and linearized epitopes on the helicase domains of the MDA5 protein. The ELISA-based depletion assay suggests that anti-MDA5 autoantibodies specifically target each of the three helicase domains. Twenty-two of the 24 serum samples showed reactivity in the in-house ELISA and all 22 displayed reactivity towards the helicase domains of the MDA5 protein.
conclusionsOur data revealed that the main immunogenic targets of anti-MDA5 autoantibodies from MDA5(+) patients are the helicase domains. Considering that the helicase domains are responsible for the enzymatic activity and subsequent triggering of an inflammatory response, our findings suggest that binding of anti-MDA5 autoantibodies could alter the canonical activity of the MDA5 protein and potentially affect the downstream induction of a pro-inflammatory cascade.
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