Autosomal dominant gain of function STAT1 mutation and severe bronchiectasis - 09/10/17
, Hagit Daum b, Malena Cohen-Cymberknoh a, Susanne Unger c, d, David Shoseyov a, Polina Stepensky e, Baerbel Keller c, Klaus Warnatz c, Eitan Kerem aAbstract |
Background |
In a substantial number of patients with non-cystic fibrosis (CF) bronchiectasis an etiology cannot be found. Various complex immunodeficiency syndromes account for a significant portion of these patients but the mechanism elucidating the predisposition for suppurative lung disease often remains unknown.
Objective |
To investigate the cause and mechanism predisposing a patient to severe bronchiectasis.
Methods |
A patient presenting with severe non-CF bronchiectasis was investigated. Whole exome analysis (WES) was performed and complemented by extensive immunophenotyping.
Results |
The genetic analysis revealed an autosomal dominant gain-of-function mutation (AD- GOF) in the signal transducer and activator of transcription 1 (STAT1) in the patient. STAT1 phosphorylation studies showed increased phosphorylation of STAT1 after stimulation with interferon γ (IFN-γ). Immunophenotyping showed normal counts of CD4 and CD8 T cells, B and NK cells, but a reduction of all memory B cells especially class switched memory B cells. Minor changes in the CD8 T cell subpopulations were seen.
Conclusions |
Early use of WES in the investigation of non-CF bronchiectasis was highly advantageous. The degree of impairment in class-switched memory B cells may predispose patients with AD- GOF mutations in STAT1 to suppurative sinopulmonary disease.
Le texte complet de cet article est disponible en PDF.Highlights |
• | AD-GOF mutations in STAT1 may cause sinopulmonary disease in a subset of patients. |
• | Impairment in class-switched memory B cells is present in these patients. |
• | The mechanism linking the B-cell dysfunction to the STAT1 mutation is unknown. |
• | The impairment in memory B cells may correlate to the sinopulmonary disease. |
Keywords : Bronchiectasis, Chronic mucocutaneous candidiasis, Autosomal dominant gain-of-function STAT1 mutations (AD-GOF STAT1 mutations), Memory B cells
Plan
Vol 126
P. 39-45 - mai 2017 Retour au numéro
Article précédent
- Home-made spacer as an auxiliary device in administration of beclomethasone via pressurized metered dose inhaler for asthma control. A randomized controlled pragmatic trial
- Deborah Schor, José Ângelo Rizzo, Decio Medeiros, Ana Carolina Dela Bianca, Almerinda Rego Silva, Carlos Nunes, Mário Morais-Almeida, Emanuel Sarinho
- What's the secret behind the benefits of whole-body vibration training in patients with COPD? A randomized, controlled trial
- Rainer Gloeckl, Inga Jarosch, Ulrike Bengsch, Magdalena Claus, Tessa Schneeberger, Vasileios Andrianopoulos, Jeffrey W. Christle, Wolfgang Hitzl, Klaus Kenn
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?