Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia. - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Journal of Experimental Medicine Année : 2015

Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia.

Emmanuel Laplantine

Résumé

Inherited, complete deficiency of human HOIL-, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylo-pectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A patient with multiorgan autoinflammation, combined immunodeficiency, subclinical amylopectinosis, and systemic lymphangiectasia, is homozygous for a mutation in HOIP, the gene encoding the catalytic component of LUBAC. The missense allele (L72P, in the PUB domain) is at least severely hypomorphic, as it impairs HOIP expression and destabilizes the whole LUBAC complex. Linear ubiquitination and NF-kB activation are impaired in the patient's fibroblasts stimulated by IL-1 or TNF. In contrast, the patient's monocytes respond to IL-1 more vigorously than control mono-cytes. However, the activation and differentiation of the patient's B cells are impaired in response to CD40 engagement. These cellular and clinical phenotypes largely overlap those of HOIL-deficient patients. Clinical differences between HOIL-and HOIP-mutated patients may result from differences between the mutations, the loci, or other factors. Our findings show that human HOIP is essential for the assembly and function of LUBAC and for various processes governing inflammation and immunity in both hematopoietic and nonhematopoietic cells.
Fichier principal
Vignette du fichier
J Exp Med-2015-Boisson-jem.20141130.pdf (2.38 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

pasteur-01158038 , version 1 (29-05-2015)

Licence

Paternité - Pas d'utilisation commerciale - Partage selon les Conditions Initiales

Identifiants

Citer

Bertrand Boisson, Emmanuel Laplantine, Kerry Dobbs, Aurélie Cobat, Nadine Tarantino, et al.. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia.. Journal of Experimental Medicine, 2015, ⟨10.1084/jem.20141130⟩. ⟨pasteur-01158038⟩
1118 Consultations
383 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More