Single-cell sequencing reveals distinct peripheral immune responses in anti-MDA5 antibody positive dermatomyositis with rapidly progressive interstitial lung disease
Authors' conclusion
This study demonstrates that antiviral response plays an important role in the pathogenesis of MDA5+ DM with RPILD, as well as changes in downstream immune pathways
Study context
- Population
- Patients with MDA5+ DM with rapidly progressive interstitial lung disease (RPILD) or ILD and healthy controls
- Participants
- 4 / 3 / 3
- Comparison
- MDA5+ DM with RPILD vs MDA5+ DM with ILD vs healthy controls
- MDA5+ DM with RPILDn = 4
- non-RPILDn = 3
- Healthy controls (HCs)n = 3reference
- Outcome
- Peripheral immune landscape (single-cell RNA sequencing (scRNA-seq) of PBMCs)
Methodological detailssingle-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs)
- Single-cell RNA sequencing of PBMCs
Main finding
As reported in the abstract
- CD14+ monocyte proportion increased; NK cell, CD4+ T cell and CD8+ T cell proportions decreased in MDA5+ DM with RPILD vs HCs
- Obvious antiviral response the main feature of MDA5+ DM with RPILD, with increased expression of RIG-I pathway interferon-stimulated genes (ISGs) (IRF7, DDX60, IFI27, IFI6)
- Antiviral response not significant in MDA5+ DM with ILD
- Multiple immune pathways downregulated in RPILD: antigen processing and presentation, translation initiation, mRNA splicing, T and B cell activation
- Multiple signalling pathways, including MHC-I and MHC-II, attenuated in RPILD
- MHC-II signalling absent in CD4+ naïve T cells from RPILD
Original publication
Single-cell sequencing reveals distinct peripheral immune responses in anti-MDA5 antibody positive dermatomyositis with rapidly progressive interstitial lung disease. Arthritis Res Ther. Published 8 October 2025. doi:10.
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