Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling.
10 affiliations
- 1State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
- 2Department of Nephrology, Rheumatology and Immunology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, China.
- 3Department of Rheumatology, Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- 4Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, China.
- 5Life Sciences Institute, Zhejiang University , Hangzhou, China.
- 6Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
- 7Liangzhu Laboratory of Zhejiang University School of Medicine, Hangzhou, China.
- 8Department of Hematology, The Affiliated Children's Hospital of Xiangya School of Medicine, Central South University (Hunan Children's Hospital), Changsha, China.
- 9Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
- 10Department of Rheumatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
NBAS deficiency is a multisystem disorder, but its immunologic manifestations and underlying mechanisms remain poorly defined. Here, we expand the genotypic and phenotypic spectrum of NBAS deficiency through four patients carrying five loss-of-function NBAS mutations. Minigene assays and RNA analysis showed that these splicing or missense mutations resulted in aberrant alternative splicing. Clinically, the patients showed early-onset recurrent or persistent cytopenias and immune dysregulation, together with severe infections, inflammatory activation, and multi-organ involvement, including renal and neurologic manifestations. Transcriptomic analysis revealed overactivation of type I interferon signaling pathways compared with healthy controls, and single-cell RNA sequencing demonstrated that this upregulated inflammation was predominantly driven by myeloid cells. Together, these findings identify NBAS deficiency as a cause of immune dysregulation characterized by myeloid-driven type I interferonopathy, expand the clinical spectrum of NBAS-related disorders, and highlight the critical role of NBAS in maintaining immune homeostasis.
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BibTeX
@article{liu2026deficiency,
title = {{Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling.}},
author = {Chenlu Liu and Liang Zhang and Meiping Lu and Yunyan Shen and Yuhao Yao and Fei Liu and Qintao Wang and Benshan Zhang and Li Guo and Xiaozhong Li and Qing Zhou and Jianhua Mao and Xiaomin Yu},
journal = {Journal of human immunity},
year = {2026},
month = oct,
doi = {10.70962/jhi.20260018},
url = {https://europepmc.org/article/MED/42949555},
note = {CC BY},
}
RIS
TY - JOUR
TI - Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling.
AU - Chenlu Liu
AU - Liang Zhang
AU - Meiping Lu
AU - Yunyan Shen
AU - Yuhao Yao
AU - Fei Liu
AU - Qintao Wang
AU - Benshan Zhang
AU - Li Guo
AU - Xiaozhong Li
AU - Qing Zhou
AU - Jianhua Mao
AU - Xiaomin Yu
PY - 2026
DA - 2026/10/28
JO - Journal of human immunity
DO - 10.70962/jhi.20260018
UR - https://europepmc.org/article/MED/42949555
AB - NBAS deficiency is a multisystem disorder, but its immunologic manifestations and underlying mechanisms remain poorly defined. Here, we expand the genotypic and phenotypic spectrum of NBAS deficiency through four patients carrying five loss-of-function NBAS mutations. Minigene assays and RNA analysis showed that these splicing or missense mutations resulted in aberrant alternative splicing. Clinically, the patients showed early-onset recurrent or persistent cytopenias and immune dysregulation, together with severe infections, inflammatory activation, and multi-organ involvement, including renal and neurologic manifestations. Transcriptomic analysis revealed overactivation of type I interferon signaling pathways compared with healthy controls, and single-cell RNA sequencing demonstrated that this upregulated inflammation was predominantly driven by myeloid cells. Together, these findings identify NBAS deficiency as a cause of immune dysregulation characterized by myeloid-driven type I interferonopathy, expand the clinical spectrum of NBAS-related disorders, and highlight the critical role of NBAS in maintaining immune homeostasis.
SN - 3065-8993
ER -