An early-onset SLE patient with a novel paternal inherited BACH2 mutation

作者全名："Zhou, Lina; Sun, Gan; Chen, Ran; Chen, Junjie; Fang, Shuyu; Xu, Qiling; Tang, Wenjing; Dai, Rongxin; Zhang, Zhiyong; An, Yunfei; Tang, Xuemei; Zhao, Xiaodong"

作者地址："[Zhou, Lina; Sun, Gan; Chen, Ran; Chen, Junjie; Fang, Shuyu; Xu, Qiling; Tang, Wenjing; Dai, Rongxin; Zhang, Zhiyong; An, Yunfei; Tang, Xuemei; Zhao, Xiaodong] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Infect & Immun, Childrens Hosp,Minist Educ,Key Lab Child Dev & Dis, Chongqing, Peoples R China; [Tang, Wenjing; Dai, Rongxin; Zhang, Zhiyong; An, Yunfei; Tang, Xuemei] Chongqing Med Univ, Div Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Zhao, XD (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab Child Infect & Immun, Childrens Hosp,Minist Educ,Key Lab Child Dev & Dis, Chongqing, Peoples R China."

来源：JOURNAL OF CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000982789800001

JCR分区：Q1

影响因子：9.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：BACH2 deficiency; inborn error of immunity; systemic lupus erythematosus; monogenic lupus

摘要："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."

基金机构：General Basic Research Project from the Ministry of Education Key Laboratory of Child Development and Disorders [GBRP-202119]; Graduate Mentor Team of Chongqing Municipal Education Commission [201909-66]

基金资助正文：This work was supported by the General Basic Research Pro-ject 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).