Prevalence and functional characterization of anti-interferon autoantibodies in inflammatory myopathies

Objectives Functional autoantibodies targeting interferons (IFNs) can lead to immunodeficiency and have been implicated in various autoimmune diseases. Despite the critical role of interferons in myositis pathogenesis, the significance of anti-IFN autoantibodies in inflammatory myopathies remains poorly understood. This study aimed to investigate the prevalence and functional impact of anti-IFN autoantibodies in patients with myositis. Methods Serum samples from 147 patients across two independent myositis cohorts were screened for autoantibodies against IFN-α, IFN-β, IFN-ω, and IFN-γ. An independent validation cohort of 34 patients was also assessed for autoantibodies against type I IFN. Functional assays were performed to evaluate whether these autoantibodies inhibited type I IFN-induced signal transduction or protein expression. Results Increased binding to IFN-α, IFN-β, IFN-ω, and IFN-γ was detected in 3.9%, 5.5%, 2.8%, and 0.7% of patients, respectively. Their prevalence did not significantly differ among myositis subtypes. Functional assays revealed no relevant inhibitory effects on type I IFN signaling. Conclusions A subset of patients with inflammatory myopathies harbor low-level anti-IFN autoantibodies, but the absence of functional activity suggests that these autoantibodies are unlikely to directly contribute to disease pathogenesis.