A Cohort Study on Deficiency of ADA2 from China

Autor: Guo-min Li, Xu Han, Ye Wu, Wei Wang, Hong-xia Tang, Mei-ping Lu, Xue-mei Tang, Yi Lin, Fan Deng, Jun Yang, Xin-ning Wang, Cong-cong Liu, Wen-jie Zheng, Bing-bing Wu, Fang Zhou, Hong Luo, Liang Zhang, Hai-mei Liu, Wan-zhen Guan, Shi-hao Wang, Pan-feng Tao, Tai-jie Jin, Ran Fang, Yuan Wu, Jie Zhang, Yao Zhang, Tian-nan Zhang, Wei Yin, Li Guo, Wen-jing Tang, Hong Chang, Qiu-ye Zhang, Xiao-zhong Li, Jian-guo Li, Zhi-xuan Zhou, Si-rui Yang, Kang-kang Yang, Hong Xu, Hong-mei Song, Natalie T. Deuitch, Pui Y. Lee, Qing Zhou, Li Sun
Rok vydání: 2023
Předmět:
Zdroj: Journal of Clinical Immunology. 43:835-845
ISSN: 1573-2592
0271-9142
Popis: 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.
Databáze: OpenAIRE
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