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Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination

Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare primary immunodeficiencies characterized by the lack of switched isotype (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with abnormal somatic hypermutation. Analysis of CSR deficiencies has helped...

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Autores principales: Péron, Sophie, Metin, Ayse, Gardès, Pauline, Alyanakian, Marie-Alexandra, Sheridan, Eamonn, Kratz, Christian Peter, Fischer, Alain, Durandy, Anne
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571921/
https://www.ncbi.nlm.nih.gov/pubmed/18824584
http://dx.doi.org/10.1084/jem.20080789
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author Péron, Sophie
Metin, Ayse
Gardès, Pauline
Alyanakian, Marie-Alexandra
Sheridan, Eamonn
Kratz, Christian Peter
Fischer, Alain
Durandy, Anne
author_facet Péron, Sophie
Metin, Ayse
Gardès, Pauline
Alyanakian, Marie-Alexandra
Sheridan, Eamonn
Kratz, Christian Peter
Fischer, Alain
Durandy, Anne
author_sort Péron, Sophie
collection PubMed
description Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare primary immunodeficiencies characterized by the lack of switched isotype (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with abnormal somatic hypermutation. Analysis of CSR deficiencies has helped reveal the key functions of CSR-triggering molecules, i.e., CD40L, CD40, and effector molecules such as activation-induced cytidine deaminase and uracil N-glycosylase. We report a new form of B cell–intrinsic CSR deficiency found in three patients with deleterious, homozygous mutations in the gene encoding the PMS2 component of the mismatch repair machinery. CSR was found partially defective in vivo and markedly impaired in vitro. It is characterized by the defective occurrence of double-strand DNA breaks (DSBs) in switch regions and abnormal formation of switch junctions. This observation strongly suggests a role for PMS2 in CSR-induced DSB generation.
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spelling pubmed-25719212009-04-27 Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination Péron, Sophie Metin, Ayse Gardès, Pauline Alyanakian, Marie-Alexandra Sheridan, Eamonn Kratz, Christian Peter Fischer, Alain Durandy, Anne J Exp Med Brief Definitive Reports Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare primary immunodeficiencies characterized by the lack of switched isotype (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with abnormal somatic hypermutation. Analysis of CSR deficiencies has helped reveal the key functions of CSR-triggering molecules, i.e., CD40L, CD40, and effector molecules such as activation-induced cytidine deaminase and uracil N-glycosylase. We report a new form of B cell–intrinsic CSR deficiency found in three patients with deleterious, homozygous mutations in the gene encoding the PMS2 component of the mismatch repair machinery. CSR was found partially defective in vivo and markedly impaired in vitro. It is characterized by the defective occurrence of double-strand DNA breaks (DSBs) in switch regions and abnormal formation of switch junctions. This observation strongly suggests a role for PMS2 in CSR-induced DSB generation. The Rockefeller University Press 2008-10-27 /pmc/articles/PMC2571921/ /pubmed/18824584 http://dx.doi.org/10.1084/jem.20080789 Text en © Péron 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.jem.org/misc/terms.shtml). 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 Brief Definitive Reports
Péron, Sophie
Metin, Ayse
Gardès, Pauline
Alyanakian, Marie-Alexandra
Sheridan, Eamonn
Kratz, Christian Peter
Fischer, Alain
Durandy, Anne
Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
title Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
title_full Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
title_fullStr Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
title_full_unstemmed Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
title_short Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination
title_sort human pms2 deficiency is associated with impaired immunoglobulin class switch recombination
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2571921/
https://www.ncbi.nlm.nih.gov/pubmed/18824584
http://dx.doi.org/10.1084/jem.20080789
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