Dergi makalesi Açık Erişim
Leiding, Jennifer W.; Vogel, Tiphanie P.; Santarlas, Valentine G. J.; Mhaskar, Rahul; Smith, Madison R.; Carisey, Alexandre; Vargas-Hernandez, Alexander; Silva-Carmona, Manuel; Heeg, Maximilian; Rensing-Ehl, Anne; Neven, Benedicte; Hadjadj, Jerome; Hambleton, Sophie; Leahy, Timothy Ronan; Meesilpavikai, Kornvalee; Cunningham-Rundles, Charlotte; Dutmer, Cullen M.; Sharapova, Svetlana O.; Taskinen, Mervi; Chua, Ignatius
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J." }, { "affiliation": "Univ S Florida, Dept Internal Med, Morsani Coll Med, Tampa, FL USA", "name": "Mhaskar, Rahul" }, { "name": "Smith, Madison R." }, { "affiliation": "St Jude Childrens Res Hosp, Dept Cell & Mol Biol, Memphis, TN USA", "name": "Carisey, Alexandre" }, { "name": "Vargas-Hernandez, Alexander" }, { "affiliation": "Texas Childrens Hosp, Baylor Coll Med, Dept Pediat, Houston, TX USA", "name": "Silva-Carmona, Manuel" }, { "affiliation": "Univ Freiburg, Med Ctr, Fac Med, Inst Immunodeficiency,Ctr Chron Immunodeficiency, Freiburg, Germany", "name": "Heeg, Maximilian" }, { "affiliation": "Univ Freiburg, Med Ctr, Fac Med, Inst Immunodeficiency,Ctr Chron Immunodeficiency, Freiburg, Germany", "name": "Rensing-Ehl, Anne" }, { "affiliation": "Inst Imagine, INSERM, UMR 1163, Lab Immunogenet Pediat Autoimmune Dis, Paris, France", "name": "Neven, Benedicte" }, { "affiliation": "Inst Imagine, INSERM, UMR 1163, Lab Immunogenet Pediat Autoimmune Dis, Paris, France", "name": "Hadjadj, Jerome" }, { "affiliation": "Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, Tyne & Wear, England", "name": "Hambleton, Sophie" }, { "affiliation": "Childrens Hlth Ireland Crumlin, Dublin, Ireland", "name": "Leahy, Timothy Ronan" }, { "name": "Meesilpavikai, Kornvalee" }, { "affiliation": "Mt Sinai Sch Med, Dept Med, New York, NY USA", "name": "Cunningham-Rundles, Charlotte" }, { "affiliation": "Univ Colorado, Sch Med, Childrens Hosp Colorado, Aurora, CO USA", "name": "Dutmer, Cullen M." }, { "affiliation": "Belarusian Res Ctr Pediat Oncol Hematol & Immunol, Minsk, BELARUS", "name": "Sharapova, Svetlana O." }, { "name": "Taskinen, Mervi" }, { "name": "Chua, Ignatius" } ], "description": "<p>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. (J Allergy Clin Immunol 2023;151:1081-95.)</p>", "doi": "10.1016/j.jaci.2022.09.002", "has_grant": false, "journal": { "issue": "4", "pages": "15", "title": "JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY", "volume": "151" }, "license": { "id": "cc-by" }, "publication_date": "2023-01-01", "relations": { "version": [ { "count": 1, "index": 0, "is_last": true, "last_child": { "pid_type": "recid", "pid_value": "269722" }, "parent": { "pid_type": "recid", "pid_value": "269721" } } ] }, "resource_type": { "subtype": "article", "title": "Dergi makalesi", "type": "publication" }, "science_branches": [ "Di\u011fer" ], "title": "Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome" }, "owners": [ 1 ], "revision": 1, "stats": { "downloads": 0.0, "unique_downloads": 0.0, "unique_views": 0.0, "version_downloads": 0.0, "version_unique_downloads": 0.0, "version_unique_views": 0.0, "version_views": 0.0, "version_volume": 0.0, "views": 0.0, "volume": 0.0 }, "updated": "2024-06-07T14:02:56.732278+00:00" }
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