Multicenter international cohort study of haploinsufficiency of A20 reveals novel genetic architecture and phenotypic evolution.

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Title: Multicenter international cohort study of haploinsufficiency of A20 reveals novel genetic architecture and phenotypic evolution.
Authors: He T; Department of Rheumatology and Immunology, Shenzhen Children's Hospital, Shenzhen University, Shenzhen, China; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Wang J; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China., Carpio Tumba M; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Wang S; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Cell and Molecular Biology Laboratory, Affiliated Zhoushan Hospital of Wenzhou Medical University, Wenzhou, China; Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China., Luo Y; Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China., Chen J; Department of Gastroenterology, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China., Li G; National Children's Medical Center, Shanghai, China; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Shu Z; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Zhang S; Department of Pediatric, Allergy Immune and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Research Center for Child Health, Guangzhou, China., Stone DL; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., Huang Y; Department of Rheumatology and Immunology, Shenzhen Children's Hospital, Shenzhen University, Shenzhen, China., Lv Q; National Children's Medical Center, Shanghai, China; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Xiong W; Department of Rheumatology and Immunology, Shenzhen Children's Hospital, Shenzhen University, Shenzhen, China., Wang J; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China., Yu Z; Department of Pediatrics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Cuff CV; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Kairis E; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Kethri A; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Towheed A; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Goyette K; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa., Karri U; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa; Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, Pa., Wang J; Department of Biostatistics and Health Data Science, School of Public Health, University of Pittsburgh, Pittsburgh, Pa., Liu C; Department of Biostatistics and Health Data Science, School of Public Health, University of Pittsburgh, Pittsburgh, Pa., Romeo T; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., Alsina L; Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu and Institut de Recerca Sant Joan de Déu, and the Universitat de Barcelona, Barcelona, Spain., Rosenberg DL; University of Wisconsin School of Medicine and Public Health, Madison, Wis., Clemente D; Pediatric Rheumatology Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain., López-Robledillo JC; Pediatric Rheumatology Unit, Hospital Infantil Universitario Niño Jesús, Madrid, Spain., Rong Z; The Second Hospital of Hebei Medical University, Shijiazhuang, China., Zhao X; The Second Hospital of Hebei Medical University, Shijiazhuang, China., Jiang L; The Second Hospital of Hebei Medical University, Shijiazhuang, China., Aldave-Becerra JC; Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru., Muñoz-Urribarri AB; Hospital Nacional Edgardo Rebagliati Martins, Lima, Peru., Oommen PT; Department of Pediatric Oncology, Hematology and Clinical Immunology, Division of Pediatric Rheumatology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany., Campbell-Stokes P; Child Health Service, Hutt Hospital, National Pediatric Rheumatology Service, Te Whatu Ora, New Zealand., Zhu M; Department of Rheumatology and Immunology, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, China., Liu P; Department of Pediatric Intensive Care Unit, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Guo L; Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Xu Y; Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yu Z; Department of Nephrology, Rheumatology and Immunology, Fujian Children's Hospital, Fuzhou, China., Tong H; Department of Nephrology, Rheumatology and Immunology, Fujian Children's Hospital, Fuzhou, China., Qiu X; Department of Nephrology, Rheumatology and Immunology, Fujian Children's Hospital, Fuzhou, China., Zhang Y; Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Chen H; Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Zhang C; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China., Ou J; Department of Pediatric Rheumatology and Immunology, Zhongshan Boai Hospital, Zhongshan, China., Liu C; Department of Pediatric Rheumatology, Immunology & Allergy, Children's Medical Center, The First Hospital of Jilin University, Changchun, China., Liu J; Department of Pediatric Rheumatology, Immunology & Allergy, Children's Medical Center, The First Hospital of Jilin University, Changchun, China., Shen Y; Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, China., Cao J; Department of Pediatric Intensive Care Unit of Hunan Children's Hospital, Changsha, China., Zhang X; Department of Pediatric Intensive Care Unit of Hunan Children's Hospital, Changsha, China., Yang K; Department of Pediatric Rheumatology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China., Bao Y; Department of Pediatric Nephrology, Xi'an Children's Hospital, The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, China., Li Z; Department of Pediatric Nephrology, Xi'an Children's Hospital, The Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, China., Cao J; Department of General Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China., Duan Y; Department of General Medicine, Children's Hospital of Chongqing Medical University, Chongqing, China., Liu F; Children's Hospital of Hebei, Shijiazhuang, China., Shi B; Department of Pediatric Intensive Care Unit (PICU), Maternal and Child Health Hospital of Hubei Province, Wuhan, China., Sun M; Department of Neonatology, Children's Hospital of Hebei, Shijiazhuang, China., Ma L; Department of Neonatology, Children's Hospital of Hebei, Shijiazhuang, China., Chen Y; Department of Pediatric Endocrinology and Genetic Metabolism, Henan Children's Hospital, Zhengzhou, China., Yang W; Department of Pediatric Endocrinology and Genetic Metabolism, Henan Children's Hospital, Zhengzhou, China., Han X; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China., Ma S; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China., Luo J; Pediatric Department, The Affiliated Suzhou Hospital of Nanjing University Medical School, Suzhou, China., Gu W; Chigene (Beijing) Translational Medical Research Center Co Ltd, Beijing Quanpu Medical Laboratory Co, Ltd, Beijing, China., Yu G; Chigene (Beijing) Translational Medical Research Center Co Ltd, Beijing Quanpu Medical Laboratory Co, Ltd, Beijing, China., Shi W; Department of Digestive Diseases, Hebei Children's Hospital, Shijiazhuang, China., Zhao R; Department of Digestive Diseases, Hebei Children's Hospital, Shijiazhuang, China., Sun L; Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Li W; Department of Infectious Disease, Children's Hospital of Hebei Province, Shijiazhuang, China., An Y; Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Tang X; Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Zhao X; Department of Rheumatology and Immunology, Children's Hospital of Chongqing Medical University, Chongqing, China., Han T; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Ma J; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Li Y; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Piao Y; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Sun F; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Zhang D; Children's Hospital of Hebei, Shijiazhuang, China., Yin M; Children's Hospital of Hebei, Shijiazhuang, China., Zheng S; Department of Rheumatology and Immunology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China., Li T; Department of Rheumatology and Immunology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China., Niu H; The First Department of General Surgery, Hebei Children's Hospital, Shijiazhuang, China., Lin L; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China., Mei S; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China., Zhou F; Henan Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China., Yang S; Department of Pediatric Rheumatology, Immunology & Allergy, Children's Medical Center, The First Hospital of Jilin University, Changchun, China., Li D; First Affiliated Hospital of Xinjiang Medical University, Wulumuqi, China., Yan M; First Affiliated Hospital of Xinjiang Medical University, Wulumuqi, China., Zeng H; Department of Pediatric, Allergy Immune and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Research Center for Child Health, Guangzhou, China., Zeng P; Department of Pediatric, Allergy Immune and Rheumatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Research Center for Child Health, Guangzhou, China., Zheng W; Department of Pediatric Rheumatology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China., Li X; Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou, China., Li X; Department of Pediatric Rheumatology and Immunology, Zhongshan Boai Hospital, Zhongshan, China., Liu Y; Department of Pediatric Rheumatology and Immunology, Zhongshan Boai Hospital, Zhongshan, China., Huang L; Department of Pediatric Rheumatology and Immunology, Zhongshan Boai Hospital, Zhongshan, China., Yu H; Department of Rheumatology and Immunology, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, China., Fan Z; Department of Rheumatology and Immunology, The Affiliated Children's Hospital of Nanjing Medical University, Nanjing, China., Shen M; Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Ministry of Science & Technology, State Key Laboratory of Complex Severe and Rare Diseases, PUMCH, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China., Lu M; Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Fang Z; Department of Rheumatology Immunology and Allergy, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China., Rimland CA; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, and Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Mass., Song H; Department of Pediatrics, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China., Peterson LW; Division of Rheumatology & Immunology, Department of Pediatrics, Washington University in St Louis, St Louis, Mo., Yousuf Al-Nesf MA; Adult Allergy and Immunology Division, Hamad Medical Corporation, Doha, Qatar., Aqel S; Adult Allergy and Immunology Division, Hamad Medical Corporation, Doha, Qatar., Mudawi DS; Adult Allergy and Immunology Division, Hamad Medical Corporation, Doha, Qatar., Raje N; Children's Mercy Kansas City, University of Missouri Kansas City, Kansas City, Mo., Slowik V; Children's Mercy Kansas City, University of Missouri Kansas City, Kansas City, Mo., Harris JG; Children's Mercy Kansas City, University of Missouri Kansas City, Kansas City, Mo., Snyder B; Children's Mercy Kansas City, University of Missouri Kansas City, Kansas City, Mo., Scheffler-Mendoza S; Servicio de Inmunología Clínica, Instituto Nacional de Pediatría, Mexico City, Mexico., Yamazaki-Nakashimada MA; Servicio de Inmunología Clínica, Instituto Nacional de Pediatría, Mexico City, Mexico., Cooper MA; Division of Rheumatology & Immunology, Department of Pediatrics, Washington University in St Louis, St Louis, Mo., Lau YL; Department of Pediatrics and Adolescent Medicine, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China., Cetin Gedik K; University of Pittsburgh, UPMC Children's Hospital of Pittsburgh, Division of Pediatric Rheumatology, Pittsburgh, Pa., Wang W; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Ying W; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Hou J; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Zhou Q; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Sun B; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Sun J; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Wang X; Department of Clinical Immunology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Ombrello AK; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., Huang Y; Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Wu HL; Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China., Sun L; National Children's Medical Center, Shanghai, China; Department of Rheumatology, Children's Hospital of Fudan University, Shanghai, China., Mao H; Department of Immunology, Ministry of Education Key Laboratory of Major Diseases in Children, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China., Yu X; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China., Liu Z; National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China., Aksentijevich I; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., Kastner DL; Inflammatory Disease Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., Schwartz DM; University of Pittsburgh, Departments of Medicine and Immunology, Division of Rheumatology, Pittsburgh, Pa. Electronic address: daniella.schwartz@pitt.edu., Yang J; Department of Rheumatology and Immunology, Shenzhen Children's Hospital, Shenzhen University, Shenzhen, China. Electronic address: rogasansz@163.com., Zhou Q; Liangzhu Laboratory, Zhejiang University, Hangzhou, China; Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Life Sciences Institute, Zhejiang University, Hangzhou, China. Electronic address: zhouqingnwu@gmail.com.
Source: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2026 Jun; Vol. 157 (6), pp. 1395-1410. Date of Electronic Publication: 2026 Feb 13.
Publication Type: Journal Article; Multicenter Study
Journal Info: Publisher: Mosby Country of Publication: United States NLM ID: 1275002 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-6825 (Electronic) Linking ISSN: 00916749 NLM ISO Abbreviation: J Allergy Clin Immunol Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:1097-6825
DOI:10.1016/j.jaci.2026.02.002