A subtype of multiple sclerosis defined by an activated immune defense program
Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- a...
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| Veröffentlicht in: | Genes and immunity 2006-09, Vol.7 (6), p.522-531 |
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| creator | van Baarsen, L G M van der Pouw Kraan, T C T M Kragt, J J Baggen, J M C Rustenburg, F Hooper, T Meilof, J F Fero, M J Dijkstra, C D Polman, C H Verweij, C L |
| description | Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS. |
| doi_str_mv | 10.1038/sj.gene.6364324 |
| format | Article |
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In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/sj.gene.6364324</identifier><identifier>PMID: 16837931</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Care and treatment ; Case-Control Studies ; Causes of ; Cluster Analysis ; DNA microarrays ; Gene Expression ; Gene Expression Regulation ; Genetic aspects ; Genetic Heterogeneity ; Genomics ; Human Genetics ; Humans ; Immune response ; Immune system ; Immunoglobulins ; Immunology ; Interferon ; Interferon Type I - immunology ; Interferon Type I - metabolism ; Magnetic resonance imaging ; Multiple sclerosis ; Multiple Sclerosis, Relapsing-Remitting - blood ; Multiple Sclerosis, Relapsing-Remitting - genetics ; Multiple Sclerosis, Relapsing-Remitting - immunology ; Oligonucleotide Array Sequence Analysis ; original-article ; Peripheral blood ; Physiological aspects ; Poxviridae Infections - genetics ; Signal Transduction ; Transcription ; Up-Regulation ; Viruses</subject><ispartof>Genes and immunity, 2006-09, Vol.7 (6), p.522-531</ispartof><rights>Springer Nature Limited 2006</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2006</rights><rights>Springer Nature Limited 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-ace622b0b7dc5b73066c43378cba9a882f500f3291f7f11d7846bbbf66bb73013</citedby><cites>FETCH-LOGICAL-c586t-ace622b0b7dc5b73066c43378cba9a882f500f3291f7f11d7846bbbf66bb73013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.gene.6364324$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.gene.6364324$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16837931$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van Baarsen, L G M</creatorcontrib><creatorcontrib>van der Pouw Kraan, T C T M</creatorcontrib><creatorcontrib>Kragt, J J</creatorcontrib><creatorcontrib>Baggen, J M C</creatorcontrib><creatorcontrib>Rustenburg, F</creatorcontrib><creatorcontrib>Hooper, T</creatorcontrib><creatorcontrib>Meilof, J F</creatorcontrib><creatorcontrib>Fero, M J</creatorcontrib><creatorcontrib>Dijkstra, C D</creatorcontrib><creatorcontrib>Polman, C H</creatorcontrib><creatorcontrib>Verweij, C L</creatorcontrib><title>A subtype of multiple sclerosis defined by an activated immune defense program</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>Given the heterogeneous nature of multiple sclerosis (MS), we applied DNA microarray technology to determine whether variability is reflected in peripheral blood (PB) cells. In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.</description><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Case-Control Studies</subject><subject>Causes of</subject><subject>Cluster Analysis</subject><subject>DNA microarrays</subject><subject>Gene Expression</subject><subject>Gene Expression Regulation</subject><subject>Genetic aspects</subject><subject>Genetic Heterogeneity</subject><subject>Genomics</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Interferon</subject><subject>Interferon Type I - immunology</subject><subject>Interferon Type I - metabolism</subject><subject>Magnetic resonance imaging</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - blood</subject><subject>Multiple Sclerosis, Relapsing-Remitting - genetics</subject><subject>Multiple Sclerosis, Relapsing-Remitting - immunology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>original-article</subject><subject>Peripheral blood</subject><subject>Physiological aspects</subject><subject>Poxviridae Infections - genetics</subject><subject>Signal Transduction</subject><subject>Transcription</subject><subject>Up-Regulation</subject><subject>Viruses</subject><issn>1466-4879</issn><issn>1476-5470</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFktuL1DAUxoso7kWffVKKC4IPnU2aNJfHYfGysCh4eQ5JelI6tOmYpIvz35syo8OIixTSJOd3vpOTfEXxAqMVRkRcx82qAw8rRhglNX1UnGPKWdVQjh4vc8YqKrg8Ky5i3CCEGWbyaXGGmSBcEnxefFqXcTZpt4VycuU4D6nfDlBGO0CYYh_LFlzvoS3NrtS-1Db19zrldT-Os4clDD5CuQ1TF_T4rHji9BDh-eF_WXx__-7bzcfq7vOH25v1XWUbwVKlLbC6Nsjw1jaGE8SYpYRwYY2WWojaNQg5UkvsuMO45YIyY4xjecw0JpfFm71urvtjhpjU2EcLw6A9THNULGtIhOR_QSwFQ4jUGbz6C9xMc_C5CVUzinktGGWZev0ghYXEVDb0KNXpAVTv3ZSCtktdtcb5XDWibCm4-geVvxbG3k4-33veP0l4e5KQmQQ_U6fnGNXt1y-n7PWetfkVYwCntqEfddgpjNTiHBU3anGOOjgnZ7w6dDabEdojf7BKBtAeiDnkOwjH1h_WfLlP8TrNAf5o_o7_AqpK1ak</recordid><startdate>200609</startdate><enddate>200609</enddate><creator>van Baarsen, L G M</creator><creator>van der Pouw Kraan, T C T M</creator><creator>Kragt, J J</creator><creator>Baggen, J M C</creator><creator>Rustenburg, F</creator><creator>Hooper, T</creator><creator>Meilof, J F</creator><creator>Fero, M J</creator><creator>Dijkstra, C D</creator><creator>Polman, C H</creator><creator>Verweij, C L</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7U9</scope><scope>7X8</scope></search><sort><creationdate>200609</creationdate><title>A subtype of multiple sclerosis defined by an activated immune defense program</title><author>van Baarsen, L G M ; van der Pouw Kraan, T C T M ; Kragt, J J ; Baggen, J M C ; Rustenburg, F ; Hooper, T ; Meilof, J F ; Fero, M J ; Dijkstra, C D ; Polman, C H ; Verweij, C L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c586t-ace622b0b7dc5b73066c43378cba9a882f500f3291f7f11d7846bbbf66bb73013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Case-Control Studies</topic><topic>Causes of</topic><topic>Cluster Analysis</topic><topic>DNA microarrays</topic><topic>Gene Expression</topic><topic>Gene Expression Regulation</topic><topic>Genetic aspects</topic><topic>Genetic Heterogeneity</topic><topic>Genomics</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunoglobulins</topic><topic>Immunology</topic><topic>Interferon</topic><topic>Interferon Type I - immunology</topic><topic>Interferon Type I - metabolism</topic><topic>Magnetic resonance imaging</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - blood</topic><topic>Multiple Sclerosis, Relapsing-Remitting - genetics</topic><topic>Multiple Sclerosis, Relapsing-Remitting - immunology</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>original-article</topic><topic>Peripheral blood</topic><topic>Physiological aspects</topic><topic>Poxviridae Infections - genetics</topic><topic>Signal Transduction</topic><topic>Transcription</topic><topic>Up-Regulation</topic><topic>Viruses</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van Baarsen, L G M</creatorcontrib><creatorcontrib>van der Pouw Kraan, T C T M</creatorcontrib><creatorcontrib>Kragt, J J</creatorcontrib><creatorcontrib>Baggen, J M C</creatorcontrib><creatorcontrib>Rustenburg, F</creatorcontrib><creatorcontrib>Hooper, T</creatorcontrib><creatorcontrib>Meilof, J F</creatorcontrib><creatorcontrib>Fero, M J</creatorcontrib><creatorcontrib>Dijkstra, C D</creatorcontrib><creatorcontrib>Polman, C H</creatorcontrib><creatorcontrib>Verweij, C L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>MEDLINE - 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In this study, we studied whole-blood gene expression profiles of 29 patients with relapsing-remitting MS (RRMS) and 25 age- and sex-matched healthy controls. We used microarrays with a complexity of 43K cDNAs. The data were analyzed using sophisticated pathway-level analysis in order to provide insight into the deregulated peripheral immune response programs in MS. We found a remarkable elevated expression of a spectrum of genes known to be involved in immune defense in the PB of MS patients compared to healthy individuals. Cluster analysis revealed that the increased expression of these genes was characteristic for approximately half of the patients. In addition, the gene signature in this group of patients was comparable with a virus response program. We conclude that the transcriptional signature of the PB cells reflects the heterogeneity of MS and defines a sub-population of RRMS patients, who exhibit an activated immune defense program that resembles a virus response program, which is supportive for a link between viruses and MS.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16837931</pmid><doi>10.1038/sj.gene.6364324</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomedical and Life Sciences Biomedicine Cancer Research Care and treatment Case-Control Studies Causes of Cluster Analysis DNA microarrays Gene Expression Gene Expression Regulation Genetic aspects Genetic Heterogeneity Genomics Human Genetics Humans Immune response Immune system Immunoglobulins Immunology Interferon Interferon Type I - immunology Interferon Type I - metabolism Magnetic resonance imaging Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - blood Multiple Sclerosis, Relapsing-Remitting - genetics Multiple Sclerosis, Relapsing-Remitting - immunology Oligonucleotide Array Sequence Analysis original-article Peripheral blood Physiological aspects Poxviridae Infections - genetics Signal Transduction Transcription Up-Regulation Viruses |
| title | A subtype of multiple sclerosis defined by an activated immune defense program |
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