دورية أكاديمية
Somatic Mosaic NLRP3 Mutations and Inflammasome Activation in Late-Onset Chronic Urticaria
| العنوان: | Somatic Mosaic NLRP3 Mutations and Inflammasome Activation in Late-Onset Chronic Urticaria |
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| المؤلفون: | Assrawi, Eman, Louvrier, Camille, Lepelletier, Clémence, Georgin-Lavialle, Sophie, Bouaziz, Jean-David, Awad, Fawaz, Moinet, Florence, Moguelet, Philippe, Vignon-Pennamen, Marie Dominique, Piterboth, William, Jumeau, Claire, Cobret, Laetitia, El Khouri, Elma, Copin, Bruno, Duquesnoy, Philippe, Legendre, Marie, Grateau, Gilles, Karabina, Sonia A., Amselem, Serge, Giurgea, Irina |
| المساهمون: | Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau APHP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hopital Saint-Louis AP-HP (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Tenon AP-HP, Al-Quds University, CHU de la Martinique Fort de France, FA was supported by Alquds University in Palestine and from the “Fondation pour la Recherche Médicale”, France (FDT20130928419). EA was supported by An-Najah University in Palestine.CLo was supported by INSERM, France (Poste d’accueil, 00552404), ANR-17-CE17-0021,FMFgeneToDiag,Fièvre Méditerranéenne Familiale (FMF) et maladies apparentées : des bases moléculaires et cellulaires à la mise au point de tests diagnostiques(2017) |
| المصدر: | ISSN: 0022-202X. |
| بيانات النشر: | HAL CCSD Nature Publishing Group |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | [SDV]Life Sciences [q-bio], [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.IMM]Life Sciences [q-bio]/Immunology |
| الوصف: | International audience ; Chronic urticaria is a common skin disorder with heterogeneous causes. In the absence of physical triggers, chronic urticarial rash is called idiopathic or spontaneous. The objective of this study was to identify the molecular and cellular bases of a disease condition displayed by two unrelated patients aged over 60 years who presented for two decades with a chronic urticaria resistant to standard therapy that occurred in the context of systemic inflammation not triggered by cold. In both patients, a targeted sequencing approach using a next generation technology identified somatic mosaic mutations in NLRP3, a gene encoding a key inflammasome component. The study of several of both patients' cell types showed that, despite the late onset of the disease, NLRP3 mutations were not found to be restricted to myelomonocytic cells. Rather, the data obtained strongly suggested that the mutational event occurred very early, during embryonic development. As shown by functional studies, the identified mutations-an in-frame deletion and a recurrent NLRP3 missense mutation-have a gain-of-function effect on NLRP3-inflammasome activation. Consistently, a complete remission was obtained in both patients with anti-IL-1 receptor antagonists. This study unveils that in late-onset chronic urticaria, the search for autoinflammatory markers and somatic mosaic NLRP3 mutations may have important diagnostic and therapeutic consequences. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31513803; hal-03489548; https://hal.science/hal-03489548Test; https://hal.science/hal-03489548/documentTest; https://hal.science/hal-03489548/file/S0022202X19332166.pdfTest; PII: S0022-202X(19)33216-6; PUBMED: 31513803; WOS: 000520410900019 |
| DOI: | 10.1016/j.jid.2019.06.153 |
| الإتاحة: | https://doi.org/10.1016/j.jid.2019.06.153Test https://hal.science/hal-03489548Test https://hal.science/hal-03489548/documentTest https://hal.science/hal-03489548/file/S0022202X19332166.pdfTest |
| حقوق: | http://creativecommons.org/licenses/by-ncTest/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.532532A0 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.jid.2019.06.153 |
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