1 Ocak 2023 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

Dublin Core

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  <dc:creator>Leiding, Jennifer W.</dc:creator>
  <dc:creator>Vogel, Tiphanie P.</dc:creator>
  <dc:creator>Santarlas, Valentine G. J.</dc:creator>
  <dc:creator>Mhaskar, Rahul</dc:creator>
  <dc:creator>Smith, Madison R.</dc:creator>
  <dc:creator>Carisey, Alexandre</dc:creator>
  <dc:creator>Vargas-Hernandez, Alexander</dc:creator>
  <dc:creator>Silva-Carmona, Manuel</dc:creator>
  <dc:creator>Heeg, Maximilian</dc:creator>
  <dc:creator>Rensing-Ehl, Anne</dc:creator>
  <dc:creator>Neven, Benedicte</dc:creator>
  <dc:creator>Hadjadj, Jerome</dc:creator>
  <dc:creator>Hambleton, Sophie</dc:creator>
  <dc:creator>Leahy, Timothy Ronan</dc:creator>
  <dc:creator>Meesilpavikai, Kornvalee</dc:creator>
  <dc:creator>Cunningham-Rundles, Charlotte</dc:creator>
  <dc:creator>Dutmer, Cullen M.</dc:creator>
  <dc:creator>Sharapova, Svetlana O.</dc:creator>
  <dc:creator>Taskinen, Mervi</dc:creator>
  <dc:creator>Chua, Ignatius</dc:creator>
  <dc:date>2023-01-01</dc:date>
  <dc:description>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.)</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/269722</dc:identifier>
  <dc:identifier>oai:aperta.ulakbim.gov.tr:269722</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY 151(4) 15</dc:source>
  <dc:title>Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
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