Interferon-related gene expression defines disease activity, organ involvement and treatment response in juvenile dermatomyositis

Abstract Objectives To evaluate the relationship between interferon-related gene (IRG) expression and disease activity, organ involvement and serological subgroups in juvenile dermatomyositis (JDM), and to assess its potential as a biomarker for disease monitoring and treatment response. Methods Patients with JDM enrolled in a single-centre cohort were assessed using standardised clinical measures, including physician’s global assessment (PGA), Childhood Myositis Assessment Scale (CMAS), Manual Muscle Testing (MMT8) and modified skin Disease Activity Score. Associations between IRG expression and clinical features were analysed using correlation analyses and mixed-effects models. Longitudinal trajectories of disease activity were explored using latent class mixed models. Results Seventy-four patients contributed 158 samples. Expression of type-I IRGs (IFI27, IFI44L, IFIT1, RSAD2, SIGLEC1) and CXCL10 was significantly higher in active disease and correlated with muscle and skin disease activity. IRG expression inversely correlated with CMAS and MMT8 and positively with mDAS. Distinct organ-specific associations were identified: CXCL9 expression was associated with interstitial lung disease, while IL-18 was associated with calcinosis, cutaneous ulceration and gastrointestinal involvement. Higher IRG expression was observed in patients with anti-MDA5 and anti-NXP2 autoantibodies. Longitudinal analyses demonstrated that IRG expression paralleled disease activity trajectories and decreased in patients achieving inactive disease, including those treated with baricitinib. Conclusion Interferon pathway activation is closely associated with disease activity and organ involvement in JDM. IRG expression reflects dynamic changes in disease status and may serve as a clinically useful biomarker for monitoring disease activity, stratifying patients by organ involvement and supporting response assessment to targeted therapies.