Type I Interferonopathies in Inborn Errors of Immunity: Pathogenesis, Clinical phenotype, Diagnosis and Management.
Zeinali Fatemeh F, Rezaei Nima N, Yazdani Reza R
Type I interferonopathies represent a heterogeneous group of inborn errors of immunity (IEI), characterized by dysregulated and persistent activation of the Type I interferon pathway. These patients present a broad spectrum of clinical phenotypes involving the nervous system, skin, lungs, and haematopoietic system. Diagnosis is often challenging owing to overlap with other autoinflammatory and autoimmune conditions. In parallel with the expanding molecular spectrum of these disorders, their classification within IEI has continued to evolve. This review provides an updated synthesis of Type I interferonopathies in the context of the 2024 International Union of Immunological Societies (IUIS) classification, linking the underlying genetic defects and dysregulated interferon pathways to their characteristic and overlapping clinical phenotypes. Particular emphasis is placed on a practical diagnostic framework integrating clinical recognition, interferon-based biomarkers, and molecular testing, as well as on the transition from conventional immunomodulation toward pathway-directed therapies, including the growing clinical experience with Janus kinase inhibitors. This review integrates current knowledge on the pathogenesis, clinical features, diagnostic approaches, and treatment strategies in patients with Type I interferonopathies, providing an updated clinically oriented framework for their recognition, diagnosis, and management within the expanding spectrum of IEIs.