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Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia
Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. We report the clinical description and molecular analysis of a novel inherited disorder of the human LUBAC complex. A...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451137/ https://www.ncbi.nlm.nih.gov/pubmed/26008899 http://dx.doi.org/10.1084/jem.20141130 |
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author | Boisson, Bertrand Laplantine, Emmanuel Dobbs, Kerry Cobat, Aurélie Tarantino, Nadine Hazen, Melissa Lidov, Hart G.W. Hopkins, Gregory Du, Likun Belkadi, Aziz Chrabieh, Maya Itan, Yuval Picard, Capucine Fournet, Jean-Christophe Eibel, Hermann Tsitsikov, Erdyni Pai, Sung-Yun Abel, Laurent Al-Herz, Waleed Casanova, Jean-Laurent Israel, Alain Notarangelo, Luigi D. |
author_facet | Boisson, Bertrand Laplantine, Emmanuel Dobbs, Kerry Cobat, Aurélie Tarantino, Nadine Hazen, Melissa Lidov, Hart G.W. Hopkins, Gregory Du, Likun Belkadi, Aziz Chrabieh, Maya Itan, Yuval Picard, Capucine Fournet, Jean-Christophe Eibel, Hermann Tsitsikov, Erdyni Pai, Sung-Yun Abel, Laurent Al-Herz, Waleed Casanova, Jean-Laurent Israel, Alain Notarangelo, Luigi D. |
author_sort | Boisson, Bertrand |
collection | PubMed |
description | Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. 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-κB activation are impaired in the patient’s fibroblasts stimulated by IL-1β or TNF. In contrast, the patient’s monocytes respond to IL-1β more vigorously than control monocytes. 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-1-deficient patients. Clinical differences between HOIL-1- 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. |
format | Online Article Text |
id | pubmed-4451137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44511372015-12-01 Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia Boisson, Bertrand Laplantine, Emmanuel Dobbs, Kerry Cobat, Aurélie Tarantino, Nadine Hazen, Melissa Lidov, Hart G.W. Hopkins, Gregory Du, Likun Belkadi, Aziz Chrabieh, Maya Itan, Yuval Picard, Capucine Fournet, Jean-Christophe Eibel, Hermann Tsitsikov, Erdyni Pai, Sung-Yun Abel, Laurent Al-Herz, Waleed Casanova, Jean-Laurent Israel, Alain Notarangelo, Luigi D. J Exp Med Article Inherited, complete deficiency of human HOIL-1, a component of the linear ubiquitination chain assembly complex (LUBAC), underlies autoinflammation, infections, and amylopectinosis. 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-κB activation are impaired in the patient’s fibroblasts stimulated by IL-1β or TNF. In contrast, the patient’s monocytes respond to IL-1β more vigorously than control monocytes. 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-1-deficient patients. Clinical differences between HOIL-1- 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. The Rockefeller University Press 2015-06-01 /pmc/articles/PMC4451137/ /pubmed/26008899 http://dx.doi.org/10.1084/jem.20141130 Text en © 2015 Boisson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Boisson, Bertrand Laplantine, Emmanuel Dobbs, Kerry Cobat, Aurélie Tarantino, Nadine Hazen, Melissa Lidov, Hart G.W. Hopkins, Gregory Du, Likun Belkadi, Aziz Chrabieh, Maya Itan, Yuval Picard, Capucine Fournet, Jean-Christophe Eibel, Hermann Tsitsikov, Erdyni Pai, Sung-Yun Abel, Laurent Al-Herz, Waleed Casanova, Jean-Laurent Israel, Alain Notarangelo, Luigi D. Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
title | Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
title_full | Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
title_fullStr | Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
title_full_unstemmed | Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
title_short | Human HOIP and LUBAC deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
title_sort | human hoip and lubac deficiency underlies autoinflammation, immunodeficiency, amylopectinosis, and lymphangiectasia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451137/ https://www.ncbi.nlm.nih.gov/pubmed/26008899 http://dx.doi.org/10.1084/jem.20141130 |
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