Somatic Mosaic NLRP3 Mutations and Inflammasome Activation in Late-Onset Chronic Urticaria
Eman Assrawi
(1)
,
Camille Louvrier
(1, 2)
,
Clémence Lepelletier
(3)
,
Sophie Georgin-Lavialle
(1, 4)
,
Jean-David Bouaziz
(3)
,
Fawaz Awad
(1, 5)
,
Florence Moinet
(6)
,
Philippe Moguelet
(4)
,
Marie Dominique Vignon-Pennamen
(3)
,
William Piterboth
(2)
,
Claire Jumeau
(1)
,
Laetitia Cobret
(1)
,
Elma El Khouri
(1)
,
Bruno Copin
(2)
,
Philippe Duquesnoy
(1)
,
Marie Legendre
(1, 2)
,
Gilles Grateau
(1, 4)
,
Sonia A. Karabina
(1)
,
Serge Amselem
(1, 2)
,
Irina Giurgea
(1, 2)
Eman Assrawi
- Fonction : Auteur
- PersonId : 1250467
- IdHAL : eman-assrawi
- ORCID : 0000-0001-8449-2281
Camille Louvrier
- Fonction : Auteur
- PersonId : 1183907
- IdHAL : camille-louvrier
- ORCID : 0000-0003-2105-1117
Sophie Georgin-Lavialle
- Fonction : Auteur
- PersonId : 764309
- IdHAL : sophie-georgin-lavialle
- ORCID : 0000-0001-6668-8854
- IdRef : 111766311
Jean-David Bouaziz
- Fonction : Auteur
- PersonId : 772315
- ORCID : 0000-0002-4993-2461
William Piterboth
- Fonction : Auteur
- PersonId : 1175358
- IdHAL : williampiterboth
- ORCID : 0000-0002-0704-2428
Claire Jumeau
- Fonction : Auteur
- PersonId : 1187865
- IdHAL : claire-jumeau
Marie Legendre
- Fonction : Auteur
- PersonId : 1147534
- IdHAL : marie-legendre
- ORCID : 0000-0003-2178-0846
Sonia A. Karabina
- Fonction : Auteur
- PersonId : 1165750
- IdHAL : sonia-athina-karabina
- ORCID : 0000-0002-5588-5710
- IdRef : 183282574
Serge Amselem
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 936326
- IdHAL : serge-amselem
- ORCID : 0000-0001-9506-3968
- IdRef : 066957761
Connectez-vous pour contacter l'auteur
Irina Giurgea
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 854037
- IdHAL : irina-giurgea
- ORCID : 0000-0002-5035-2958
- IdRef : 17474711X
Connectez-vous pour contacter l'auteur
Résumé
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.
Format du dépôt | Fichier |
---|---|
Type de dépôt | Article dans une revue |
Résumé |
en
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.
|
Titre |
en
Somatic Mosaic NLRP3 Mutations and Inflammasome Activation in Late-Onset Chronic Urticaria
|
Auteur(s) |
Eman Assrawi
1
, Camille Louvrier
1, 2
, Clémence Lepelletier
3
, Sophie Georgin-Lavialle
1, 4
, Jean-David Bouaziz
3
, Fawaz Awad
1, 5
, Florence Moinet
6
, Philippe Moguelet
4
, Marie Dominique Vignon-Pennamen
3
, William Piterboth
2
, Claire Jumeau
1
, Laetitia Cobret
1
, Elma El Khouri
1
, Bruno Copin
2
, Philippe Duquesnoy
1
, Marie Legendre
1, 2
, Gilles Grateau
1, 4
, Sonia A. Karabina
1
, Serge Amselem
1, 2
, Irina Giurgea
1, 2
1
U933 -
Maladies génétiques d'expression pédiatrique
( 1081006 )
- UF de Génétique clinique et moléculaire
Sorbonne Université
AP-HP Hôpital d'Enfants Armand-Trousseau
26 avenue du Docteur Arnold Netter
75012 PARIS CEDEX 12
- France
2
CHU Trousseau [APHP]
( 360410 )
- 26 Avenue du Dr Arnold Netter, 75012 Paris
- France
3
AP-HP -
Hopital Saint-Louis [AP-HP]
( 506757 )
- 1 Avenue Claude Vellefaux, 75010 Paris
- France
4
CHU Tenon [AP-HP]
( 328304 )
- 4 Rue de la Chine, 75020 Paris
- France
5
Al-Quds University
( 442999 )
- East Jerusalem - Abu Dis
- Territoires palestiniens
6
CHU de la Martinique [Fort de France]
( 360604 )
- CS 90632 – 97261 Fort de France Cedex
Martinique
- Martinique
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Licence |
Paternité - Pas d'utilisation commerciale
|
Langue du document |
Anglais
|
Nom de la revue |
|
Date de publication |
2020-04-30
|
Volume |
140
|
Page/Identifiant |
791 - 798.e2
|
Projet(s) ANR |
|
Financement |
|
Domaine(s) |
|
DOI | 10.1016/j.jid.2019.06.153 |
PII | S0022-202X(19)33216-6 |
Pubmed Id | 31513803 |
UT key WOS | 000520410900019 |
Origine :
Fichiers produits par l'(les) auteur(s)
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