The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis

Area of Science:

• Immunology
• Rheumatology
• Dermatology

Background:

• The type 1 interferon (IFN) pathway is known to be upregulated in dermatomyositis (DM).
• Understanding the factors associated with systemic type I IFN activity is crucial for managing DM.
• Previous research has indicated a role for type I IFNs in the pathogenesis of autoimmune diseases.

Purpose of the Study:

• To define the independent associations of organ-specific disease activity, autoantibodies, and clinical factors with systemic type I IFN activity in adult DM patients.
• To investigate the relationship between type I IFN scores and clinical manifestations in DM.
• To explore the potential of type I IFN blockade as a therapeutic strategy.

Main Methods:

• RNA sequencing was performed on 355 whole blood samples from 202 well-phenotyped DM patients.
• A 13-gene type I IFN score was modeled using cross-sectional and longitudinal clinical data.
• Statistical analyses were employed to assess associations between the type I IFN score and various clinical and serologic variables.

Main Results:

• The type I IFN transcriptional response pattern in DM was similar to that observed in systemic lupus erythematosus.
• Type I IFN scores were associated with specific autoantibodies, such as anti-melanoma differentiation-associated protein 5 (anti-MDA-5) and anti-Mi-2.
• The type I IFN score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti-MDA-5 antibodies.

Conclusions:

• The type I IFN score is independently linked to skin and muscle disease activity, and specific clinical/serologic features in DM.
• The type I IFN score strongly correlates with skin disease activity, even after accounting for muscle disease and anti-MDA-5 status.
• These findings provide evidence supporting type I IFN blockade as a viable therapeutic strategy for dermatomyositis.