Abstract
BACH2-related immunodeficiency and autoimmunity (BRIDA) is an inborn error of immunity, newly reported in 2017, presenting with symptoms of immunoglobulin deficiency and ongoing colitis. Studies using a mouse model have demonstrated that BACH2 deficiency predisposes individuals to systemic lupus erythematosus (SLE); however, no BACH2 deficiency has been reported in SLE patients. Here we describe a patient with BRIDA presenting with early-onset SLE, juvenile dermatomyositis, and IgA deficiency. Whole exome sequencing analysis of the patient and her parents revealed a novel heterozygous point mutation in BACH2, c.G1727T, resulting in substitution of a highly conserved arginine with leucine (R576L), which is predicted to be deleterious, in the patient and her father. Reduced BACH2 expression and deficient transcriptional repression of the BACH2 target, BLIMP1, were detected in PBMCs or lymphoblastoid cell lines of our patient. Notably, extreme reduction of memory B cells was detected in the patient’s father, although he had no obvious symptoms. SLE symptoms and recurrent fever were relieved by treatment with prednisone combined with tofacitinib. Thus, we present the second report of BRIDA and demonstrate that BACH2 may be a monogenic cause of SLE.
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Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgments
We thank the patient and her families for participating in this study. We also thank the doctors, nurses, and other health care providers at the Children’s Hospital of Chongqing Medical University.
Funding
This work was supported by the General Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders (No. GBRP-202119) and Graduate Mentor Team of Chongqing Municipal Education Commission (grant number 2019–09-66).
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Xiaodong Zhao and Lina Zhou designed experiments. Lina Zhou analyzed the data and wrote the first draft of the manuscript and performed the experiments. Gan Sun contributed to construction of Plasmids. Ran Chen contributed to design and perform the analyzation of somatic hypermutation. Junjie Chen participated in the detection of lymphocyte subsets. Shuyu Fang and Qiling Xu contributed to the RNA was extraction. Wenjing Tang, Rongxin Dai, Zhiyong Zhang, Yunfei An and Xuemei Tang contributed to treatment and regular follow-up of the patient, as well as revision of the manuscript. Xiaodong Zhao supervised the research and revised the manuscript. All authors contributed to the article and approved the submitted version.
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The study was performed following Declaration of Helsinki and approved by the Institutional Review Board of Children’s Hospital of Chongqing Medical University (2021–138).
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Zhou, L., Sun, G., Chen, R. et al. An early-onset SLE patient with a novel paternal inherited BACH2 mutation. J Clin Immunol 43, 1367–1378 (2023). https://doi.org/10.1007/s10875-023-01506-7
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DOI: https://doi.org/10.1007/s10875-023-01506-7