دورية أكاديمية
أعرض في EDS

Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS.

التفاصيل البيبلوغرافية
العنوان: Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS.
المؤلفون: van der Made CI; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Potjewijd J; Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands., Hoogstins A; Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Willems HPJ; Department of Internal Medicine, Maxima Medisch Centrum, Eindhoven, The Netherlands., Kwakernaak AJ; Department of Internal Medicine and Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, location AMC/Meibergdreef, Amsterdam, The Netherlands., de Sevaux RGL; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands., van Daele PLA; Department of Internal Medicine and Department of Immunology, Erasmus Medical Center, Rotterdam, The Netherlands., Simons A; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., Heijstek M; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Beck DB; National Human Genome Research Institute, National Institutes of Health, Bethesda, Md., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., van Paassen P; Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands., Elizabeth Hak A; Department of Internal Medicine and Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, location AMC/Meibergdreef, Amsterdam, The Netherlands., van der Veken LT; Department of Genetics, Division Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., van Gijn ME; Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Hoischen A; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands., van de Veerdonk FL; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands., Leavis HL; Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands., Rutgers A; Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. Electronic address: A.Rutgers@umcg.nl.
المصدر: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2022 Jan; Vol. 149 (1), pp. 432-439.e4. Date of Electronic Publication: 2021 May 25.
نوع المنشور: Case Reports; Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: 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
أسماء مطبوعة: Original Publication: St Louis, Mosby.
مواضيع طبية MeSH: Hereditary Autoinflammatory Diseases/*genetics , Myelodysplastic Syndromes/*genetics , Skin Diseases, Genetic/*genetics , Ubiquitin-Activating Enzymes/*genetics, Adult ; Age of Onset ; Aged ; Hereditary Autoinflammatory Diseases/diagnosis ; Humans ; Male ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/diagnosis ; Netherlands ; Retrospective Studies ; Skin Diseases, Genetic/diagnosis
مستخلص: Background: A novel autoinflammatory syndrome was recently described in male patients who harbored somatic mutations in the X-chromosomal UBA1 gene. These patients were characterized by adult-onset, treatment-refractory inflammation with fever, cytopenia, dysplastic bone marrow, vacuoles in myeloid and erythroid progenitor cells, cutaneous and pulmonary inflammation, chondritis, and vasculitis, which is abbreviated as VEXAS.
Objective: This study aimed to (retrospectively) diagnose VEXAS in patients who had previously been registered as having unclassified autoinflammation. We furthermore aimed to describe clinical experiences with this multifaceted, complex disease.
Methods: A systematic reanalysis of whole-exome sequencing data from a cohort of undiagnosed patients with autoinflammation from academic hospitals in The Netherlands was performed. When no sequencing data were available, targeted Sanger sequencing was applied in cases with high clinical suspicion of VEXAS.
Results: A total of 12 male patients who carried mutations in UBA1 were identified. These patients presented with adult-onset (mean age 67 years, range 47-79 years) autoinflammation with systemic symptoms, elevated inflammatory parameters, and multiorgan involvement, most typically involving the skin and bone marrow. Novel features of VEXAS included interstitial nephritis, cardiac involvement, stroke, and intestinal perforation related to treatment with tocilizumab. Although many types of treatment were initiated, most patients became treatment-refractory, with a high mortality rate of 50%.
Conclusion: VEXAS should be considered in the differential diagnosis of males with adult-onset autoinflammation characterized by systemic symptoms and multiorgan involvement. Early diagnosis can prevent unnecessary diagnostic procedures and provide better prognostic information and more suitable treatment options, including stem cell transplantation.
(Copyright © 2021. Published by Elsevier Inc.)
فهرسة مساهمة: Keywords: UBA1; VEXAS; autoinflammation; somatic variants
المشرفين على المادة: 0 (UBA1 protein, human)
EC 6.2.1.45 (Ubiquitin-Activating Enzymes)
SCR Disease Name: VEXAS syndrome
تواريخ الأحداث: Date Created: 20210528 Date Completed: 20220303 Latest Revision: 20220303
رمز التحديث: 20240628
DOI: 10.1016/j.jaci.2021.05.014
PMID: 34048852
قاعدة البيانات: MEDLINE
الوصف
تدمد:1097-6825
DOI:10.1016/j.jaci.2021.05.014