Novel USP18 mutations lead to severe interferonopathy responsive to JAK inhibitor
Novel biallelic mutations of USP18 lead to excessive type I IFN responses and severe interferonopathy. Our findings highlight a novel pathogenic mechanism in which impaired ISG15 binding compromises the regulatory function of USP18. The favorable clinical response to ruxolitinib suggests a promising therapeutic strategy.
Authors
- Yiying Dou
- Qintao Wang (ORCID: https://orcid.org/0000-0001-7105-9198)
- Jianming Lai (ORCID: https://orcid.org/0000-0001-6721-4810)
- Jia Zhu (ORCID: https://orcid.org/0000-0002-8782-1818)
- Xiaogang Li (ORCID: https://orcid.org/0000-0001-9255-7559)
- Qing Zhou (ORCID: https://orcid.org/0000-0003-0290-1286)
- Xiangwei Sun
- Xiaomin Yu (ORCID: https://orcid.org/0000-0002-6981-5772)
Institutions
- Sir Run Run Shaw Hospital (CN)
- Beijing Children’s Hospital (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-09-04
- DOI
- https://doi.org/10.3389/fimmu.2025.1646996
- Primary Topic
- Cytokine Signaling Pathways and Interactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Zhejiang University
- National Key Research and Development Program of China