A Cohort Study on Deficiency of ADA2 from China

作者全名："Li, Guo-min; Han, Xu; Wu, Ye; Wang, Wei; Tang, Hong-xia; Lu, Mei-ping; Tang, Xue-mei; Lin, Yi; Deng, Fan; Yang, Jun; Wang, Xin-ning; Liu, Cong-cong; Zheng, Wen-jie; Wu, Bing-bing; Zhou, Fang; Luo, Hong; Zhang, Liang; Liu, Hai-mei; Guan, Wan-zhen; Wang, Shi-hao; Tao, Pan-feng; Jin, Tai-jie; Fang, Ran; Wu, Yuan; Zhang, Jie; Zhang, Yao; Zhang, Tian-nan; Yin, Wei; Guo, Li; Tang, Wen-jing; Chang, Hong; Zhang, Qiu-ye; Li, Xiao-zhong; Li, Jian-guo; Zhou, Zhi-xuan; Yang, Si-rui; Yang, Kang-kang; Xu, Hong; Song, Hong-mei; Deuitch, Natalie T.; Lee, Pui Y.; Zhou, Qing; Sun, Li"

作者地址："[Li, Guo-min; Wu, Bing-bing; Liu, Hai-mei; Guan, Wan-zhen; Xu, Hong; Sun, Li] Natl Childrens Med Ctr, Shanghai, Peoples R China; [Li, Guo-min; Liu, Hai-mei; Guan, Wan-zhen; Xu, Hong; Sun, Li] Fudan Univ, Dept Rheumatol, Childrens Hosp, Shanghai, Peoples R China; [Han, Xu; Wang, Shi-hao; Tao, Pan-feng; Jin, Tai-jie; Fang, Ran; Zhou, Qing] Zhejiang Univ, Life Sci Inst, Hangzhou, Peoples R China; [Wu, Ye; Wu, Yuan; Zhang, Jie; Zhang, Yao] Peking Univ First Hosp, Beijing, Peoples R China; [Wang, Wei; Zhang, Tian-nan; Song, Hong-mei] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Pediat, Beijing, Peoples R China; [Tang, Hong-xia; Yin, Wei] Huazhong Univ Sci & Technol, Wuhan Childrens Hosp, Tongji Med Coll, Wuhan, Peoples R China; [Lu, Mei-ping; Guo, Li] Zhejiang Univ, Childrens Hosp, Dept Rheumatol Immunol & Allergy, Sch Med, Hangzhou, Peoples R China; [Tang, Xue-mei; Tang, Wen-jing] Chongqing Med Univ, Dept Rheumatol & Immunol, Childrens Hosp, Chongqing, Peoples R China; [Lin, Yi; Chang, Hong; Zhang, Qiu-ye] Qingdao Univ, Affiliated Hosp, Qingdao, Peoples R China; [Deng, Fan; Li, Xiao-zhong] Childrens Hosp Soochow, Suzhou, Peoples R China; [Yang, Jun] Shenzhen Childrens Hosp, Dept Rheumatol & Immunol, Shenzhen, Peoples R China; [Wang, Xin-ning; Li, Jian-guo; Zhou, Zhi-xuan; Xu, Hong] Capital Inst Pediat, Affiliated Childrens Hosp, Beijing, Peoples R China; [Liu, Cong-cong; Yang, Si-rui] First Hosp Jilin Univ, Immunol & Allergy Dept Pediat, Div Rheumatol, Changchun, Peoples R China; [Zheng, Wen-jie; Yang, Kang-kang] Wenzhou Med Univ, Affiliated Hosp 2, Dept Rheumatol, Yuying Childrens Hosp, Wenzhou, Peoples R China; [Wu, Bing-bing] Childrens Hosp Fudan Univ, Med Transformat Ctr, Shanghai, Peoples R China; [Zhou, Fang] 960 Hosp Joint Serv Support Force Chinese Peoples, Jinan, Peoples R China; [Luo, Hong] Cent South Univ, Xiangya Hosp 2, Dept Resp Med, Changsha, Peoples R China; [Zhang, Liang] Hunan Prov Peoples Hosp, Changsha, Hunan, Peoples R China; [Deuitch, Natalie T.] Natl Human Genome Res Inst, Bethesda, MD USA; [Lee, Pui Y.] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Boston, MA USA"

通信作者："Sun, L (通讯作者)，Natl Childrens Med Ctr, Shanghai, Peoples R China.; Sun, L (通讯作者)，Fudan Univ, Dept Rheumatol, Childrens Hosp, Shanghai, Peoples R China.; Zhou, Q (通讯作者)，Zhejiang Univ, Life Sci Inst, Hangzhou, Peoples R China."

来源：JOURNAL OF CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000936007500002

JCR分区：Q1

影响因子：7.2

年份：2023

卷号：43

期号：4

开始页：835

结束页：845

文献类型：Article

关键词：Adenosine deaminase 2; Deficiency of adenosine deaminase 2; Hematology; Hematopoietic stem cell transplantation; Vasculitis; TNF inhibitors

摘要："Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi."

基金机构：　

基金资助正文：