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Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis

Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+...

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Autores principales: Hedegaard, Chris Juul, Enevold, Christian, Sellebjerg, Finn, Bendtzen, Klaus, Nielsen, Claus Henrik
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098873/
https://www.ncbi.nlm.nih.gov/pubmed/21625457
http://dx.doi.org/10.1371/journal.pone.0020253
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author Hedegaard, Chris Juul
Enevold, Christian
Sellebjerg, Finn
Bendtzen, Klaus
Nielsen, Claus Henrik
author_facet Hedegaard, Chris Juul
Enevold, Christian
Sellebjerg, Finn
Bendtzen, Klaus
Nielsen, Claus Henrik
author_sort Hedegaard, Chris Juul
collection PubMed
description Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p<0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p<0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p<0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism influences T helper (Th) cell 2- and Th17 cell responses in MNC from MS patients.
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spelling pubmed-30988732011-05-27 Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis Hedegaard, Chris Juul Enevold, Christian Sellebjerg, Finn Bendtzen, Klaus Nielsen, Claus Henrik PLoS One Research Article Variations in the gene for the nucleotide-binding oligomerisation domain (NOD) 2 have been associated with Crohn's disease but not multiple sclerosis (MS). Here we investigate the effect of three polymorphisms in the NOD2 gene (rs5743277, rs2066842 and rs5743291) on cytokine production and CD4+ T cell proliferation elicited by human myelin basic protein (MBP) in blood mononuclear cell (MNC) cultures from 29 patients with MS. No polymorphism was observed at rs5743277. No associations with the rs2066842 polymorphism were found. Concerning rs5743291, none were homozygous for the minor allele. Seven of 29 (24%) patients were heterozygous, and five of these (71%) exhibited increased MBP-induced CD4+ T cell proliferation versus four of 22 (18%), who were homozygous for the major allele (p<0.04). Interleukin (IL)-5 was induced by MBP in MNC from the same five carriers versus two (9%) homozygotes (p<0.004); four carriers (57%) versus three non-carriers (14%) exhibited IL-17 responses to MBP (p<0.04). By contrast, we found no association between the polymorphisms investigated and interferon-gamma-, tumor necrosis factor-alpha-, IL-2, -4- or IL-10 responses to MBP. These results indicate that the rs5743291 polymorphism influences T helper (Th) cell 2- and Th17 cell responses in MNC from MS patients. Public Library of Science 2011-05-20 /pmc/articles/PMC3098873/ /pubmed/21625457 http://dx.doi.org/10.1371/journal.pone.0020253 Text en Hedegaard et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hedegaard, Chris Juul
Enevold, Christian
Sellebjerg, Finn
Bendtzen, Klaus
Nielsen, Claus Henrik
Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis
title Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis
title_full Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis
title_fullStr Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis
title_full_unstemmed Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis
title_short Variation in NOD2 Augments Th2- and Th17 Responses to Myelin Basic Protein in Multiple Sclerosis
title_sort variation in nod2 augments th2- and th17 responses to myelin basic protein in multiple sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098873/
https://www.ncbi.nlm.nih.gov/pubmed/21625457
http://dx.doi.org/10.1371/journal.pone.0020253
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