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

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OBJECTIVES: Functional autoantibodies targeting 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 signalling. CONCLUSIONS: A subset of patients with inflammatory myopathies harbour low-level anti-IFN autoantibodies, but the absence of functional activity suggests that these autoantibodies are unlikely to directly contribute to disease pathogenesis.

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