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

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{
  "DOI": "10.1016/j.jaci.2022.09.002", 
  "abstract": "<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>", 
  "author": [
    {
      "family": "Leiding", 
      "given": " Jennifer W."
    }, 
    {
      "family": "Vogel", 
      "given": " Tiphanie P."
    }, 
    {
      "family": "Santarlas", 
      "given": " Valentine G. J."
    }, 
    {
      "family": "Mhaskar", 
      "given": " Rahul"
    }, 
    {
      "family": "Smith", 
      "given": " Madison R."
    }, 
    {
      "family": "Carisey", 
      "given": " Alexandre"
    }, 
    {
      "family": "Vargas-Hernandez", 
      "given": " Alexander"
    }, 
    {
      "family": "Silva-Carmona", 
      "given": " Manuel"
    }, 
    {
      "family": "Heeg", 
      "given": " Maximilian"
    }, 
    {
      "family": "Rensing-Ehl", 
      "given": " Anne"
    }, 
    {
      "family": "Neven", 
      "given": " Benedicte"
    }, 
    {
      "family": "Hadjadj", 
      "given": " Jerome"
    }, 
    {
      "family": "Hambleton", 
      "given": " Sophie"
    }, 
    {
      "family": "Leahy", 
      "given": " Timothy Ronan"
    }, 
    {
      "family": "Meesilpavikai", 
      "given": " Kornvalee"
    }, 
    {
      "family": "Cunningham-Rundles", 
      "given": " Charlotte"
    }, 
    {
      "family": "Dutmer", 
      "given": " Cullen M."
    }, 
    {
      "family": "Sharapova", 
      "given": " Svetlana O."
    }, 
    {
      "family": "Taskinen", 
      "given": " Mervi"
    }, 
    {
      "family": "Chua", 
      "given": " Ignatius"
    }
  ], 
  "container_title": "JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY", 
  "id": "269722", 
  "issue": "4", 
  "issued": {
    "date-parts": [
      [
        2023, 
        1, 
        1
      ]
    ]
  }, 
  "page": "15", 
  "title": "Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome", 
  "type": "article-journal", 
  "volume": "151"
}