Transcriptomic signatures in different tissues of anti-MDA5 positive dermatomyositis: Uncovering genes with...

Anti-melanoma differentiation-associated gene 5 antibody-positive (MDA5+) dermatomyositis (DM) is characterized by a high incidence of rapidly progressive interstitial lung disease (RP-ILD). Unique transcriptomic signatures in patients with MDA5+ DM were investigated.

Peripheral blood mononuclear cells (PBMCs), skin, and muscle biopsies from 28 patients with MDA5+/- DM were sequenced. Uniquely expressed transcripts identified using RNA sequencing analysis of PBMCs were further validated using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Receiver operating characteristic analysis was used to determine the diagnostic potential of the target genes.

In MDA5+ DM samples, components of antiviral defense, neutrophil migration, and immune-associated pathways (in PBMCs), fatty acid metabolic processes (in skin), and antigen recognition (in muscle tissue) were upregulated. The expressions of defensin alpha 3 (DEFA3), ribonuclease family member 2 (RNASE2), and interferon alpha inducible protein 27 (IFI27) were upregulated and exhibited good predictive values for RP-ILD in MDA5+ DM.

The activation of the IFN, virus-associated, and aberrant immune response pathways, as well as fatty acid metabolic processes may be involved in MDA5+ DM pathogenesis. IFI27, DEFA3, and RNASE2 may contribute to RP-ILD pathogenesis and serve as biomarkers of MDA5+ DM.