Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome.

Autor:	Leiding JW; Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore; Johns Hopkins All Children's Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St Petersburg. Electronic address: jleidin1@jhmi.edu., Vogel TP; Department of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston., Santarlas VGJ; Lake Erie College of Osteopathic Medicine, Erie., Mhaskar R; Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa., Smith MR; Department of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston., Carisey A; Department of Cell and Molecular Biology, St Jude Children's Research Hospital, Memphis., Vargas-Hernández A; Department of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston., Silva-Carmona M; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston., Heeg M; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg., Rensing-Ehl A; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg., Neven B; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163-Institut Imagine, Paris., Hadjadj J; Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR 1163-Institut Imagine, Paris., Hambleton S; Newcastle University Translational and Clinical Research Institute, Newcastle (United Kingdom)., Ronan Leahy T; Children's Health Ireland at Crumlin, Dublin., Meesilpavikai K; Department of Internal Medicine, Division of Clinical Immunology and Department of Immunology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand., Cunningham-Rundles C; Department of Medicine, Mount Sinai School of Medicine, New York., Dutmer CM; Children's Hospital Colorado, University of Colorado School of Medicine, Aurora., Sharapova SO; Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk., Taskinen M; New Children's Hospital, Pediatric Research Center, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Turku and Kuopio, Finland., Chua I; Department of Rheumatology, Immunology and Allergy, Christchurch Hospital, Christchurch; Clinical Immunogenomics Research Consortium of Australasia (CIRCA)., Hague R; Royal Hospital for Children, Glasgow., Klemann C; Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover., Kostyuchenko L; Center of Pediatric Immunology, Western Ukrainian Specialized Children's Medical Centre, Lviv., Morio T; Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo., Thatayatikom A; 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Pediatric Allergy and Immunology/Center of Investigation in Pediatrics, Faculty of Medical Sciences, State University of Campinas-Unicamp, São Paulo., O'Sullivan M; Clinical Immunogenomics Research Consortium of Australasia (CIRCA); Immunology Department, Perth Children's Hospital, Nedlands., Pachlopnik Schmid J; Division of Immunology, University Children's Hospital Zurich, Children's Research Center (CRC), Zurich., Průhová Š; Department of Pediatrics, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague., Klocperk A; Department of Immunology, Second Faculty of Medicine and University Hospital Motol, Charles University in Prague, Prague., Rees M; Department of Hematology, St Jude Children's Research Hospital, Memphis., Su H; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda., Bahna S; Allergy and Immunology Section, Louisiana State University Health Sciences Center, Shreveport., Baris S; 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Mott Children's Hospital, Michigan Medicine, Ann Arbor., Worth A; Great Ormond Street Hospital for Children, London., Seppänen MRJ; Rare Disease Center, Children's Hospital, and Adult Primary Immunodeficiency Outpatient Clinic, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki., Torgerson TR; Allen Institute, Seattle., Sogkas G; Department of Clinical Immunology and Rheumatology, Hannover Medical School, Hanover., Ehl S; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg., Tangye SG; Clinical Immunogenomics Research Consortium of Australasia (CIRCA); Garvan Institute of Medical Research, Darlinghurst; St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney., Cooper MA; Department of Pediatrics, Division of Rheumatology and Immunology, Washington University School of Medicine, St Louis., Milner JD; Department of Pediatrics, Division of Allergy and Immunology, Columbia University, New York Presbyterian Hospital, New York., Forbes Satter LR; Department of Pediatrics, Baylor College of Medicine and William T. Shearer Center for Human Immunobiology, Texas Children's Hospital, Houston. Electronic address: lisa.forbes@bcm.edu.
Jazyk:	angličtina
Zdroj:	The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2023 Apr; Vol. 151 (4), pp. 1081-1095. Date of Electronic Publication: 2022 Oct 11.
DOI:	10.1016/j.jaci.2022.09.002
Abstrakt:	Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. Conclusion: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome. (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. All rights reserved.)
Databáze:	MEDLINE
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