Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype
| dc.rights.license | open | en_US |
| dc.contributor.author | FAYAND, A. | |
| dc.contributor.author | CESCATO, M. | |
| dc.contributor.author | LE CORRE, L. | |
| dc.contributor.author | TERRÉ, A. | |
| dc.contributor.author | WACHEUX, M. | |
| dc.contributor.author | ZHU, Y.Y.J. | |
| dc.contributor.author | MELET, A. | |
| dc.contributor.author | MOREAU, T.R.J. | |
| dc.contributor.author | BODAGHI, B. | |
| hal.structure.identifier | Bordeaux population health [BPH] | |
| hal.structure.identifier | Global Health in the Global South [GHiGS] | |
| dc.contributor.author | BONNET, Fabrice | |
| dc.contributor.author | BRONNIMANN, Didier | |
| dc.contributor.author | CUISSET, L. | |
| dc.contributor.author | FARIA, R. | |
| dc.contributor.author | GRATEAU, G. | |
| dc.contributor.author | PILLET, Pascal | |
| dc.contributor.author | MULDERS-MANDERS, C.M. | |
| dc.contributor.author | NEVEN, B. | |
| dc.contributor.author | QUARTIER, P. | |
| dc.contributor.author | RICHER, Olivier | |
| dc.contributor.author | SAVEY, L. | |
| hal.structure.identifier | Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept] | |
| dc.contributor.author | TRUCHETET, Marie-Elise | |
| dc.contributor.author | PY, B.F. | |
| dc.contributor.author | BOURSIER, G. | |
| dc.contributor.author | HERBEUVAL, J.-P. | |
| dc.contributor.author | GEORGIN-LAVIALLE, S. | |
| dc.contributor.author | RODERO, M.P. | |
| dc.date.accessioned | 2024-06-13T13:27:30Z | |
| dc.date.available | 2024-06-13T13:27:30Z | |
| dc.date.issued | 2023-11 | |
| dc.identifier.issn | 0091-6749 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/200465 | |
| dc.description.abstractEn | Background: Cryopyrin-associated periodic syndrome (CAPS) is associated with NLRP3 pathogenic variants, mostly located in the NACHT (neuronal apoptosis inhibitor protein, MHC class 2 transcription activator, incompatibility locus protein from Podospora anserina, telomerase-associated protein) domain. Cold-induced urticarial rash is among the main clinical features. However, this study identified a series of 14 patients with pathogenic variants of the Y861 residue (p.Tyr861) of the LRR domain of NLRP3 and minimal prevalence of cold-induced urticarial rash. Objectives: This study aimed to address a possible genotype/phenotype correlation for patients with CAPS and to investigate at the cellular levels the impact of the Y861C substitution (p.Tyr861Cys) on NLRP3 activation. Methods: Clinical features of 14 patients with CAPS and heterozygous substitution at position 861 in the LRR domain of NLRP3 were compared to clinical features of 48 patients with CAPS and pathogenic variants outside the LRR domain of NLRP3. IL-1β secretion by PBMCs and purified monocytes from patients and healthy donors was evaluated following LPS and monosodium urate crystal stimulation. Results: Patients with substitution at position 861 of NLRP3 demonstrated a higher prevalence of sensorineural hearing loss while being less prone to skin urticarial. In contrast to patients with classical CAPS, cells from patients with a pathogenic variant at position 861 required an activation signal to secrete IL-1β but produced more IL-1β during the early and late phase of secretion than cells from healthy donors. Conclusions: Pathogenic variants of Y861 of NLRP3 drive a boost-dependent oversecretion of IL-1β associated with an atypical CAPS phenotype. © 2023 American Academy of Allergy, Asthma & Immunology | |
| dc.description.sponsorship | Dérégulation de la voie de l'interféron de type I dans la dermatomyosite juvénile: mieux comprendre la physiopathologie pour mieux identifier de nouveaux biomarqueurs pronostiques - ANR-21-CE17-0025 | en_US |
| dc.language.iso | EN | en_US |
| dc.subject.en | NLRP3 | |
| dc.subject.en | CAPS | |
| dc.subject.en | Inflammasome | |
| dc.subject.en | LRR domain | |
| dc.subject.en | Interleukin-1 | |
| dc.subject.en | Hear loss | |
| dc.subject.en | Deafness | |
| dc.subject.en | Urticaria | |
| dc.title.en | Pathogenic variants in the NLRP3 LRR domain at position 861 are responsible for a boost-dependent atypical CAPS phenotype | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.jaci.2023.07.006 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Immunologie | en_US |
| dc.identifier.pubmed | 37506976 | en_US |
| bordeaux.journal | Journal of Allergy and Clinical Immunology | en_US |
| bordeaux.page | 1303-1311.e1 | en_US |
| bordeaux.volume | 152 | en_US |
| bordeaux.hal.laboratories | ImmunoConcEpT - UMR 5164 | en_US |
| bordeaux.issue | 5 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.institution | INSERM | |
| bordeaux.team | GHIGS_BPH | |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| dc.rights.cc | Pas de Licence CC | en_US |
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