Work

Single-cell sequencing reveals distinct peripheral immune responses in anti-MDA5 antibody positive dermatomyositis with rapidly progressive interstitial lung disease

Year: 2025

Type: article

Abstract: Anti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis (MDA5 + DM) is an autoimmune disease related to rapidly progressive interstitial lung disease (RPILD) with high mortality. However, the pathogenesis of MDA5 + DM with RPILD remains unclear. We aimed to explore the peripheral immune landscape of MDA5 + DM with RPILD using single-cell RNA sequencing (scRNA-seq). We performed scRNA-seq of peripheral blood mononuclear cells (PBMCs) from MDA5 + DM with RPILD ( n = 4), MDA5 + DM with ILD (non-RPILD, n = 3), and healthy controls (HCs, n = 3). The proportion of CD14 + monocytes increased, but the proportion of natural killer cells, CD4 + T cells and CD8 + T cells decreased in MDA5 + DM with RPILD compared with HCs. Obvious antiviral response was the main feature of MDA5 + DM with RPILD, and the expression of several interferon-stimulated genes (ISGs) related to RIG-I pathway increased, including IRF7, DDX60, IFI27 and IFI6. However, this antiviral response was not significant in MDA5 + DM with ILD. In addition, multiple immune pathways were downregulated in MDA5 + DM with RPILD, including antigen processing and presentation, translation initiation, mRNA splicing, and activation of T and B cells. Cell communication analysis revealed that multiple signaling pathways, including MHC-I and MHC-II, were attenuated in MDA5 + DM with RPILD. Notably, MHC-II signaling was absent in CD4 + naïve T cells from MDA5 + DM with RPILD. 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, providing potential therapeutic targets for future treatment.

Source: Arthritis Research & Therapy

DOI: 10.1186/s13075-025-03639-z