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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...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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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. |
format | Text |
id | pubmed-2571921 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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