Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling

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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Publication Details

Journal
Journal of Human Immunity
Published
2026-10-28
DOI
https://doi.org/10.70962/jhi.20260018
Primary Topic
Immunodeficiency and Autoimmune Disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling

Fei Liu, Yunyan Shen, Meiping Lu, Qintao Wang et al.
2 links
Journal of Human Immunity
Immunodeficiency and Autoimmune Disorders
article

Deficiency of NBAS causes immune dysregulation due to hyperactivation of IFN signaling

Fei Liu, Yunyan Shen, Meiping Lu, Qintao Wang, Xiaozhong Li, Liang Zhang, Xiaomin Yu, Li Guo, Jianhua Mao, Benshan Zhang, Chenlu Liu, Yuhao Yao, Qing Zhou
article en

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.

Journal of Human ImmunityVol. 3(1)
Central South University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Sir Run Run Shaw Hospital (CN), Soochow University (CN), Children's Hospital of Zhejiang University (CN), Hunan Children's Hospital (CN), Second Affiliated Hospital of Zhejiang University (CN), Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences (CN), Zhejiang University (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, Chongqing Medical University, National Key Research and Development Program of China, Chinese Academy of Medical Sciences Initiative for Innovative Medicine, Natural Science Foundation of Zhejiang Province
Good health and well-being
Openalex Percentile: Top 19%
Immunodeficiency and Autoimmune Disorders
DOIOpen Access PDFOpenAlex
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