Objective ARF1-related disorder is a rare type I interferonopathy characterized by dysregulated interferon (IFN) signaling and chilblain-like lesions, with no established treatment. We report the clinical and immunological response to anifrolumab (ANI) in a pediatric patient. Case presentation A 9-year-old girl with a pathogenic ARF1 variant (c.295C>T, p.Arg99Cys) and severe chilblain-like lesions showed markedly elevated type I IFN activity, assessed by IFN-stimulated gene (ISG) score, monocyte CD169 expression, and plasma IFN-α levels. Following ANI initiation, the ISG score decreased within 24 hours and normalized within one month. CD169 expression and plasma IFN-α levels also normalized. Clinically, chilblain-like lesions resolved within one month, with sustained remission over 12 months. No serious adverse events were observed. Conclusion ANI led to rapid clinical improvement and normalization of multiple IFN-related biomarkers, supporting IFNAR1 blockade as a rational targeted therapy for selected patients with ARF1-related disease showing prominent type I IFN pathway activation.
Yokoyama et al. (Fri,) studied this question.