Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis
Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 w...
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| creator | Gilli, Francesca Lindberg, Raija L P Valentino, Paola Marnetto, Fabiana Malucchi, Simona Sala, Arianna Capobianco, Marco di Sapio, Alessia Sperli, Francesca Kappos, Ludwig Calogero, Raffaele A Bertolotto, Antonio |
| description | Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26).
Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to "normal" already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month.
Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies. |
| doi_str_mv | 10.1371/journal.pone.0008962 |
| format | Article |
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We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26).
Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to "normal" already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month.
Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0008962</identifier><identifier>PMID: 20126412</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Analysis ; Antigens ; Breast cancer ; CXCR4 protein ; Cytokines ; Deregulation ; Estrogens ; Female ; Gene expression ; Gene Expression Profiling ; Genes ; Genetic aspects ; Genetics and Genomics/Gene Expression ; Genomes ; Genomics ; Gestation ; Growth factors ; Growth hormones ; Humans ; Hypoxia ; Immunology/Autoimmunity ; Inflammation ; Inflammation Mediators - metabolism ; Leukocytes (mononuclear) ; Lymphocytes ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Neurobiology ; Neurological Disorders/Multiple Sclerosis and Related Disorders ; Neurosciences ; Pathogenesis ; Patients ; Peripheral blood mononuclear cells ; Placenta ; Pregnancy ; Pregnant women ; Proteins ; Transcription ; Transcription (Genetics) ; Women's health ; Women's Health/Autoimmunity, Autoimmune, and Inflammatory Diseases ; Womens health</subject><ispartof>PloS one, 2010-01, Vol.5 (1), p.e8962-e8962</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Gilli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Gilli et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-2e7ff621aad6a56891031e442e48fbca2c703178bc6a750fe1b6e2fdfde66d7c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813302/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813302/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53770,53772,79347,79348</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20126412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Kleinschnitz, Christoph</contributor><creatorcontrib>Gilli, Francesca</creatorcontrib><creatorcontrib>Lindberg, Raija L P</creatorcontrib><creatorcontrib>Valentino, Paola</creatorcontrib><creatorcontrib>Marnetto, Fabiana</creatorcontrib><creatorcontrib>Malucchi, Simona</creatorcontrib><creatorcontrib>Sala, Arianna</creatorcontrib><creatorcontrib>Capobianco, Marco</creatorcontrib><creatorcontrib>di Sapio, Alessia</creatorcontrib><creatorcontrib>Sperli, Francesca</creatorcontrib><creatorcontrib>Kappos, Ludwig</creatorcontrib><creatorcontrib>Calogero, Raffaele A</creatorcontrib><creatorcontrib>Bertolotto, Antonio</creatorcontrib><title>Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26).
Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to "normal" already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month.
Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies.</description><subject>Age</subject><subject>Analysis</subject><subject>Antigens</subject><subject>Breast cancer</subject><subject>CXCR4 protein</subject><subject>Cytokines</subject><subject>Deregulation</subject><subject>Estrogens</subject><subject>Female</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetics and Genomics/Gene Expression</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Gestation</subject><subject>Growth factors</subject><subject>Growth hormones</subject><subject>Humans</subject><subject>Hypoxia</subject><subject>Immunology/Autoimmunity</subject><subject>Inflammation</subject><subject>Inflammation Mediators - metabolism</subject><subject>Leukocytes (mononuclear)</subject><subject>Lymphocytes</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - genetics</subject><subject>Neurobiology</subject><subject>Neurological Disorders/Multiple Sclerosis and Related Disorders</subject><subject>Neurosciences</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Placenta</subject><subject>Pregnancy</subject><subject>Pregnant women</subject><subject>Proteins</subject><subject>Transcription</subject><subject>Transcription (Genetics)</subject><subject>Women's health</subject><subject>Women's Health/Autoimmunity, Autoimmune, and Inflammatory Diseases</subject><subject>Womens 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from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis</title><author>Gilli, Francesca ; Lindberg, Raija L P ; Valentino, Paola ; Marnetto, Fabiana ; Malucchi, Simona ; Sala, Arianna ; Capobianco, Marco ; di Sapio, Alessia ; Sperli, Francesca ; Kappos, Ludwig ; Calogero, Raffaele A ; Bertolotto, Antonio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c691t-2e7ff621aad6a56891031e442e48fbca2c703178bc6a750fe1b6e2fdfde66d7c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Age</topic><topic>Analysis</topic><topic>Antigens</topic><topic>Breast cancer</topic><topic>CXCR4 protein</topic><topic>Cytokines</topic><topic>Deregulation</topic><topic>Estrogens</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetics and 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of inflammation-related genes in patients with multiple sclerosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-01-29</date><risdate>2010</risdate><volume>5</volume><issue>1</issue><spage>e8962</spage><epage>e8962</epage><pages>e8962-e8962</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood.
We conducted a genome-wide transcription analysis in peripheral blood mononuclear cells (PBMCs) from 12 women (7 MS patients and 5 healthy controls) followed during their pregnancy. Samples were obtained before, during (i.e. at the third, sixth, and ninth month of gestation) and after pregnancy. A validation of the expression profiles has been conducted by using the same samples and an independent group of 25 MS patients and 11 healthy controls. Finally, considering the total group of 32 MS patients, we compared expression profiles of patients relapsing during pregnancy (n = 6) with those of relapse-free patients (n = 26).
Results showed an altered expression of 347 transcripts in non-pregnant MS patients with respect to non-pregnant healthy controls. Complementary changes in expression, occurring during pregnancy, reverted the previous imbalance particularly for seven inflammation-related transcripts, i.e. SOCS2, TNFAIP3, NR4A2, CXCR4, POLR2J, FAM49B, and STAG3L1. Longitudinal analysis showed that the overall deregulation of gene expression reverted to "normal" already within the third month of gestation, while in the post-partum gene expressions rebounded to pre-pregnancy levels. Six (18.7%) of the 32 MS patients had a relapse during pregnancy, mostly in the first trimester. The latter showed delayed expression profiles when compared to relapse-free patients: in these patients expression imbalance was reverted later in the pregnancy, i.e. at sixth month.
Specific changes in expression during pregnancy were associated with a decrease in disease activity assessed by occurrence of relapses during pregnancy. Findings might help in understanding the pathogenesis of MS and may provide basis for the development of novel therapeutic strategies.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20126412</pmid><doi>10.1371/journal.pone.0008962</doi><tpages>e8962</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_1289252106 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Analysis Antigens Breast cancer CXCR4 protein Cytokines Deregulation Estrogens Female Gene expression Gene Expression Profiling Genes Genetic aspects Genetics and Genomics/Gene Expression Genomes Genomics Gestation Growth factors Growth hormones Humans Hypoxia Immunology/Autoimmunity Inflammation Inflammation Mediators - metabolism Leukocytes (mononuclear) Lymphocytes Multiple sclerosis Multiple Sclerosis - genetics Neurobiology Neurological Disorders/Multiple Sclerosis and Related Disorders Neurosciences Pathogenesis Patients Peripheral blood mononuclear cells Placenta Pregnancy Pregnant women Proteins Transcription Transcription (Genetics) Women's health Women's Health/Autoimmunity, Autoimmune, and Inflammatory Diseases Womens health |
| title | Learning from nature: pregnancy changes the expression of inflammation-related genes in patients with multiple sclerosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-21T11%3A48%3A13IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Learning%20from%20nature:%20pregnancy%20changes%20the%20expression%20of%20inflammation-related%20genes%20in%20patients%20with%20multiple%20sclerosis&rft.jtitle=PloS%20one&rft.au=Gilli,%20Francesca&rft.date=2010-01-29&rft.volume=5&rft.issue=1&rft.spage=e8962&rft.epage=e8962&rft.pages=e8962-e8962&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0008962&rft_dat=%3Cgale_plos_%3EA473916011%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289252106&rft_id=info:pmid/20126412&rft_galeid=A473916011&rft_doaj_id=oai_doaj_org_article_6da143c805694dacb725e44629deba36&rfr_iscdi=true |