A Cohort Study on Deficiency of ADA2 from China.

Autor: Li GM; National Children's Medical Center, Shanghai, China.; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Han X; Life Sciences Institute, Zhejiang University, Hangzhou, China., Wu Y; Peking University First Hospital, Beijing, China., Wang W; Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China., Tang HX; Wuhan Children's Hospital Tongji Medical College Huazhong University of Science & Technology, Wuhan, China., Lu MP; Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Tang XM; Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Lin Y; Affiliated Hospital of Qingdao University, Qingdao, China., Deng F; The Children's Hospital of Soochow, Suzhou, China., Yang J; Department of Rheumatology and Immunology, Shenzhen Children's Hospital, Shenzhen, China., Wang XN; Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China., Liu CC; Division of Rheumatology, Immunology & Allergy in the Department of Pediatrics, The First Hospital of Jilin University, Changchun, China., Zheng WJ; Department of Rheumatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China., Wu BB; National Children's Medical Center, Shanghai, China.; Medical Transformation Centre, Children's Hospital of Fudan University, Shanghai, China., Zhou F; No. 960 Hospital of the Joint Service Support Force of the Chinese People's Liberation Army, Jinan, China., Luo H; Department of Respiratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China., Zhang L; Hunan Provincial People's Hospital, Hunan, China., Liu HM; National Children's Medical Center, Shanghai, China.; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Guan WZ; National Children's Medical Center, Shanghai, China.; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Wang SH; Life Sciences Institute, Zhejiang University, Hangzhou, China., Tao PF; Life Sciences Institute, Zhejiang University, Hangzhou, China., Jin TJ; Life Sciences Institute, Zhejiang University, Hangzhou, China., Fang R; Life Sciences Institute, Zhejiang University, Hangzhou, China., Wu Y; Peking University First Hospital, Beijing, China., Zhang J; Peking University First Hospital, Beijing, China., Zhang Y; Peking University First Hospital, Beijing, China., Zhang TN; Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China., Yin W; Wuhan Children's Hospital Tongji Medical College Huazhong University of Science & Technology, Wuhan, China., Guo L; Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Tang WJ; Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Chang H; Affiliated Hospital of Qingdao University, Qingdao, China., Zhang QY; Affiliated Hospital of Qingdao University, Qingdao, China., Li XZ; The Children's Hospital of Soochow, Suzhou, China., Li JG; Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China., Zhou ZX; Affiliated Children's Hospital of Capital Institute of Pediatrics, Beijing, China., Yang SR; Division of Rheumatology, Immunology & Allergy in the Department of Pediatrics, The First Hospital of Jilin University, Changchun, China., Yang KK; Department of Rheumatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China., Xu H; National Children's Medical Center, Shanghai, China.; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Song HM; Department of Pediatrics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China., Deuitch NT; National Human Genome Research Institute, Bethesda, MD, USA., Lee PY; Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA., Zhou Q; Life Sciences Institute, Zhejiang University, Hangzhou, China. zhouq2@zju.edu.cn., Sun L; National Children's Medical Center, Shanghai, China. lillysun@263.net.; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China. lillysun@263.net.
Jazyk: angličtina
Zdroj: Journal of clinical immunology [J Clin Immunol] 2023 May; Vol. 43 (4), pp. 835-845. Date of Electronic Publication: 2023 Feb 18.
DOI: 10.1007/s10875-023-01432-8
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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