Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency
Bertrand Boisson
(1)
,
Emmanuel Laplantine
(2)
,
Carolina Prando
(1)
,
Silvia Giliani
(3)
,
Elisabeth Israelsson
(4)
,
Zhaohui Xu
(5)
,
Avinash Abhyankar
(1)
,
Laura Israël
(6)
,
Giraldina Trevejo-Nunez
(1)
,
Dusan Bogunovic
(1)
,
Alma-Martina Cepika
(5)
,
Donna Macduff
(7)
,
Maya Chrabieh
(6)
,
Marjorie Hubeau
(6)
,
Fanny Bajolle
(8)
,
Marianne Debré
(8)
,
Evelina Mazzolari
(3)
,
Donatella Vairo
(3)
,
Fabrice Agou
(9)
,
Herbert W Virgin
(7)
,
Xavier Bossuyt
(10)
,
Caroline Rambaud
(11)
,
Fabio Facchetti
(3)
,
Damien Bonnet
(12, 8)
,
Pierre Quartier
(12, 8)
,
Jean-Christophe Fournet
(12, 8)
,
Virginia Pascual
(5)
,
Damien Chaussabel
(4, 5)
,
Luigi Notarangelo
(13)
,
Anne Puel
(6)
,
Alain Israël
(2)
,
Jean-Laurent Casanova
(1, 6, 8)
,
Capucine Picard
(6, 8)
1
Rockefeller University [New York]
2 SMAC - Signalisation Moléculaire et Activation Cellulaire
3 UniBs - Università degli Studi di Brescia = University of Brescia
4 BRI - Benaroya Research Institute [Seattle]
5 BIIR - Baylor Institute for Immunology Research
6 Inserm U980 - Génétique Humaine des Maladies Infectieuses
7 Washington University School of Medicine in St. Louis
8 CHU Necker - Enfants Malades [AP-HP]
9 Biochimie Structurale et Cellulaire
10 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
11 Hôpital Raymond Poincaré [AP-HP]
12 UPD5 - Université Paris Descartes - Paris 5
13 HMS - Harvard Medical School [Boston]
2 SMAC - Signalisation Moléculaire et Activation Cellulaire
3 UniBs - Università degli Studi di Brescia = University of Brescia
4 BRI - Benaroya Research Institute [Seattle]
5 BIIR - Baylor Institute for Immunology Research
6 Inserm U980 - Génétique Humaine des Maladies Infectieuses
7 Washington University School of Medicine in St. Louis
8 CHU Necker - Enfants Malades [AP-HP]
9 Biochimie Structurale et Cellulaire
10 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
11 Hôpital Raymond Poincaré [AP-HP]
12 UPD5 - Université Paris Descartes - Paris 5
13 HMS - Harvard Medical School [Boston]
Bertrand Boisson
- Function : Author
- PersonId : 757762
- ORCID : 0000-0001-5240-3555
- IdRef : 08188317X
Emmanuel Laplantine
- Function : Author
- PersonId : 1173009
- IdHAL : emmanuel-laplantine
- ORCID : 0000-0002-5916-4654
Carolina Prando
- Function : Author
- PersonId : 764639
- ORCID : 0000-0002-9570-9770
Dusan Bogunovic
- Function : Author
- PersonId : 807606
- ORCID : 0000-0002-9277-3232
Fabrice Agou
- Function : Author
- PersonId : 747345
- IdHAL : fabrice-agou
- ORCID : 0000-0001-6280-239X
Damien Bonnet
- Function : Author
- PersonId : 757220
- ORCID : 0000-0002-8722-5805
- IdRef : 067147569
Pierre Quartier
- Function : Author
- PersonId : 764841
- ORCID : 0000-0002-1769-549X
- IdRef : 139645683
Virginia Pascual
- Function : Author
- PersonId : 759725
- ORCID : 0000-0002-8806-8426
Damien Chaussabel
- Function : Author
- PersonId : 761494
- ORCID : 0000-0002-6131-7242
Luigi Notarangelo
- Function : Author
- PersonId : 758298
- ORCID : 0000-0002-8335-0262
Anne Puel
- Function : Author
- PersonId : 757898
- ORCID : 0000-0003-2603-0323
- IdRef : 170297969
Jean-Laurent Casanova
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 867631
Connectez-vous pour contacter l'auteur
Capucine Picard
- Function : Author
- PersonId : 758297
- ORCID : 0000-0001-8788-5056
- IdRef : 091572363
Abstract
We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin 1β (IL-1β) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB–dependent IL-1β responses differently in different cell types.