Objective

Antisynthetase syndrome (AS) and Dermatomyositis (DM) are autoimmune disorders that overlap clinically. Given the presence of DM skin lesions in AS patients, there is debate about whether AS is distinct or a subclassification of DM. Recently studies identified differences in type I interferon (IFN) between AS and DM muscle and finger eruptions. The aim of this study is to elucidate cutaneous disease pathogenic similarities and differences on a single cell level.

Methods

Five AS and seven DM patients were recruited from a prospectively collected database of well-characterized DM patients. AS patients were clinically confirmed with anti-synthetase syndrome by the Connors and Solomon et al. criteria and aminoacyl-transfer ribonucleic acid synthetase antibodies. Immunophenotyping conducted using immunofluorescence (IF) and imaging mass cytometry (IMC).

Results

IF revealed type I IFN upregulation in AS and DM compared to HC using MxA and IFNβ expression (p<0.05). IMC showed similar macrophages, T cells, B cells, and dendritic cells in AS and DM with no differences in counts (p>0.05), but an increase in myeloid dendritic cell percentage in DM (p<0.05). Key type I IFN, cytokine, and JAK-STAT pathways were similarly expressed in AS and DM (p>0.05). At a single cell level, pSTING+ macrophages in AS expressed increased TNFα, IL17, and IFNβ (p<0.001).

Conclusion

IMC is a powerful tool that identifies a role for the type I IFN system in DM-like skin lesions of AS and DM with some differences at a cellular level, but overall significant overlap exists supporting similar therapeutic decision making.