Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients
Objective To determine whether pediatric‐onset multiple sclerosis (POMS) and adults‐onset multiple sclerosis (AOMS) patients are different in initial disease severity and recovery and to investigate the associations with peripheral blood mononuclear cells (PBMCs) transcriptional profiles. Methods Cl...
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| Veröffentlicht in: | Annals of clinical and translational neurology 2021-01, Vol.8 (1), p.81-94 |
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| creator | Menascu, Shay Khavkin, Yulia Zilkha‐Falb, Rina Dolev, Mark Magalashvili, David Achiron, Anat Gurevich, Michael |
| description | Objective
To determine whether pediatric‐onset multiple sclerosis (POMS) and adults‐onset multiple sclerosis (AOMS) patients are different in initial disease severity and recovery and to investigate the associations with peripheral blood mononuclear cells (PBMCs) transcriptional profiles.
Methods
Clinical and radiological severity of first and second relapses and 6‐month recovery were analyzed in 2153 multiple sclerosis (MS) patients and compared between POMS (onset at 8–18years old) and AOMS (onset at 19–40 years old) patients. PBMCs transcriptomes of 15 POMS and 15 gender‐matched AOMS patients were analyzed 6 months after the first relapse and compared to 55 age‐matched healthy controls. Differentially Expressed Genes (DEGs) with a false discovery rate ≤ 10% were evaluated using the Partek software.
Results
POMS had increased Expanded Disability Status Scale (EDSS) score at first and second relapses, higher brain gadolinium‐enhancing T1‐lesions volume at first relapse, and more complete recovery after both relapses compared to AOMS. POMS patients, who recovered completely from the first relapse, were characterized by 19 DEGs that were mainly related to suppression of antigen presentation. Six upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls. POMS patients, who showed no recovery from the first relapse, were characterized by 28 DEGs that were mainly associated with B‐cell activation. Five upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls.
Interpretation
POMS patients may have more severe first and second relapses than AOMS. However, most often, POMS have better recovery that may be attributed to PBMCs age‐related transcriptional profiles associated with antigen presentation and B‐cell activation. |
| doi_str_mv | 10.1002/acn3.51244 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7818128</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2479378004</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4484-be81f889d982197311cc705a42dd663c76fddb6f7a02e043d4d730dc1b92e3163</originalsourceid><addsrcrecordid>eNp9kU9LBCEYxiWKiq1LHyAGukSw5avu6FyCWPoHUZc6i6tOGa5OOlPst89tK6pDFxX9-bwPz4PQHuBjwJicKB3o8QQIY2tom1Aixs0E0_Uf5y20m_MzxhiATCgnm2iLUmg4MLGN1NS74LTylQqm6pMKWSfX9S6Gcpesjq82LaouxdZ5mysXqs4ap_rk9McXZQbfV_OyuM7bKmtvU8wuV53qnQ193kEbrfLZ7n7uI_RwcX4_vRrf3F1eT89uxpoxwcYzK6AVojGNIMUcBdCa44lixJi6pprXrTGzuuUKE4sZNcxwio2GWUMshZqO0OlKtxtmc2t0mZ2Ul11yc5UWMionf78E9yQf46vkAgQQUQQOPwVSfBls7uXcZW29V8HGIUvCaqANK7kW9OAP-hyHVBJbUryhXOBicYSOVpQuieRk228zgOWyPLksT36UV-D9n_a_0a-qCgAr4K0UsfhHSp5Nb-lK9B2u5KVa</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2479378004</pqid></control><display><type>article</type><title>Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Menascu, Shay ; Khavkin, Yulia ; Zilkha‐Falb, Rina ; Dolev, Mark ; Magalashvili, David ; Achiron, Anat ; Gurevich, Michael</creator><creatorcontrib>Menascu, Shay ; Khavkin, Yulia ; Zilkha‐Falb, Rina ; Dolev, Mark ; Magalashvili, David ; Achiron, Anat ; Gurevich, Michael</creatorcontrib><description>Objective
To determine whether pediatric‐onset multiple sclerosis (POMS) and adults‐onset multiple sclerosis (AOMS) patients are different in initial disease severity and recovery and to investigate the associations with peripheral blood mononuclear cells (PBMCs) transcriptional profiles.
Methods
Clinical and radiological severity of first and second relapses and 6‐month recovery were analyzed in 2153 multiple sclerosis (MS) patients and compared between POMS (onset at 8–18years old) and AOMS (onset at 19–40 years old) patients. PBMCs transcriptomes of 15 POMS and 15 gender‐matched AOMS patients were analyzed 6 months after the first relapse and compared to 55 age‐matched healthy controls. Differentially Expressed Genes (DEGs) with a false discovery rate ≤ 10% were evaluated using the Partek software.
Results
POMS had increased Expanded Disability Status Scale (EDSS) score at first and second relapses, higher brain gadolinium‐enhancing T1‐lesions volume at first relapse, and more complete recovery after both relapses compared to AOMS. POMS patients, who recovered completely from the first relapse, were characterized by 19 DEGs that were mainly related to suppression of antigen presentation. Six upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls. POMS patients, who showed no recovery from the first relapse, were characterized by 28 DEGs that were mainly associated with B‐cell activation. Five upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls.
Interpretation
POMS patients may have more severe first and second relapses than AOMS. However, most often, POMS have better recovery that may be attributed to PBMCs age‐related transcriptional profiles associated with antigen presentation and B‐cell activation.</description><identifier>ISSN: 2328-9503</identifier><identifier>EISSN: 2328-9503</identifier><identifier>DOI: 10.1002/acn3.51244</identifier><identifier>PMID: 33197148</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Adolescent ; Adult ; Age ; Age of Onset ; Brain - pathology ; Child ; Cohort Studies ; Cytokines ; Disability Evaluation ; Disease Progression ; Female ; Gender ; Gene expression ; Genomics ; Humans ; Magnetic resonance imaging ; Male ; MicroRNAs ; Multiple sclerosis ; Multiple Sclerosis, Relapsing-Remitting - immunology ; Multiple Sclerosis, Relapsing-Remitting - pathology ; Pediatrics ; Retrospective Studies ; Severity of Illness Index ; Software ; Transcriptome ; Young Adult</subject><ispartof>Annals of clinical and translational neurology, 2021-01, Vol.8 (1), p.81-94</ispartof><rights>2020 The Authors. published by Wiley Periodicals LLC on behalf of American Neurological Association</rights><rights>2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4484-be81f889d982197311cc705a42dd663c76fddb6f7a02e043d4d730dc1b92e3163</citedby><cites>FETCH-LOGICAL-c4484-be81f889d982197311cc705a42dd663c76fddb6f7a02e043d4d730dc1b92e3163</cites><orcidid>0000-0003-1529-4876 ; 0000-0002-2020-3126</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818128/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818128/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33197148$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Menascu, Shay</creatorcontrib><creatorcontrib>Khavkin, Yulia</creatorcontrib><creatorcontrib>Zilkha‐Falb, Rina</creatorcontrib><creatorcontrib>Dolev, Mark</creatorcontrib><creatorcontrib>Magalashvili, David</creatorcontrib><creatorcontrib>Achiron, Anat</creatorcontrib><creatorcontrib>Gurevich, Michael</creatorcontrib><title>Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients</title><title>Annals of clinical and translational neurology</title><addtitle>Ann Clin Transl Neurol</addtitle><description>Objective
To determine whether pediatric‐onset multiple sclerosis (POMS) and adults‐onset multiple sclerosis (AOMS) patients are different in initial disease severity and recovery and to investigate the associations with peripheral blood mononuclear cells (PBMCs) transcriptional profiles.
Methods
Clinical and radiological severity of first and second relapses and 6‐month recovery were analyzed in 2153 multiple sclerosis (MS) patients and compared between POMS (onset at 8–18years old) and AOMS (onset at 19–40 years old) patients. PBMCs transcriptomes of 15 POMS and 15 gender‐matched AOMS patients were analyzed 6 months after the first relapse and compared to 55 age‐matched healthy controls. Differentially Expressed Genes (DEGs) with a false discovery rate ≤ 10% were evaluated using the Partek software.
Results
POMS had increased Expanded Disability Status Scale (EDSS) score at first and second relapses, higher brain gadolinium‐enhancing T1‐lesions volume at first relapse, and more complete recovery after both relapses compared to AOMS. POMS patients, who recovered completely from the first relapse, were characterized by 19 DEGs that were mainly related to suppression of antigen presentation. Six upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls. POMS patients, who showed no recovery from the first relapse, were characterized by 28 DEGs that were mainly associated with B‐cell activation. Five upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls.
Interpretation
POMS patients may have more severe first and second relapses than AOMS. However, most often, POMS have better recovery that may be attributed to PBMCs age‐related transcriptional profiles associated with antigen presentation and B‐cell activation.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Age of Onset</subject><subject>Brain - pathology</subject><subject>Child</subject><subject>Cohort Studies</subject><subject>Cytokines</subject><subject>Disability Evaluation</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gender</subject><subject>Gene expression</subject><subject>Genomics</subject><subject>Humans</subject><subject>Magnetic resonance imaging</subject><subject>Male</subject><subject>MicroRNAs</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis, Relapsing-Remitting - immunology</subject><subject>Multiple Sclerosis, Relapsing-Remitting - pathology</subject><subject>Pediatrics</subject><subject>Retrospective Studies</subject><subject>Severity of Illness Index</subject><subject>Software</subject><subject>Transcriptome</subject><subject>Young Adult</subject><issn>2328-9503</issn><issn>2328-9503</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kU9LBCEYxiWKiq1LHyAGukSw5avu6FyCWPoHUZc6i6tOGa5OOlPst89tK6pDFxX9-bwPz4PQHuBjwJicKB3o8QQIY2tom1Aixs0E0_Uf5y20m_MzxhiATCgnm2iLUmg4MLGN1NS74LTylQqm6pMKWSfX9S6Gcpesjq82LaouxdZ5mysXqs4ap_rk9McXZQbfV_OyuM7bKmtvU8wuV53qnQ193kEbrfLZ7n7uI_RwcX4_vRrf3F1eT89uxpoxwcYzK6AVojGNIMUcBdCa44lixJi6pprXrTGzuuUKE4sZNcxwio2GWUMshZqO0OlKtxtmc2t0mZ2Ul11yc5UWMionf78E9yQf46vkAgQQUQQOPwVSfBls7uXcZW29V8HGIUvCaqANK7kW9OAP-hyHVBJbUryhXOBicYSOVpQuieRk228zgOWyPLksT36UV-D9n_a_0a-qCgAr4K0UsfhHSp5Nb-lK9B2u5KVa</recordid><startdate>202101</startdate><enddate>202101</enddate><creator>Menascu, Shay</creator><creator>Khavkin, Yulia</creator><creator>Zilkha‐Falb, Rina</creator><creator>Dolev, Mark</creator><creator>Magalashvili, David</creator><creator>Achiron, Anat</creator><creator>Gurevich, Michael</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M2M</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1529-4876</orcidid><orcidid>https://orcid.org/0000-0002-2020-3126</orcidid></search><sort><creationdate>202101</creationdate><title>Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients</title><author>Menascu, Shay ; Khavkin, Yulia ; Zilkha‐Falb, Rina ; Dolev, Mark ; Magalashvili, David ; Achiron, Anat ; Gurevich, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4484-be81f889d982197311cc705a42dd663c76fddb6f7a02e043d4d730dc1b92e3163</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Age of Onset</topic><topic>Brain - pathology</topic><topic>Child</topic><topic>Cohort Studies</topic><topic>Cytokines</topic><topic>Disability Evaluation</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gender</topic><topic>Gene expression</topic><topic>Genomics</topic><topic>Humans</topic><topic>Magnetic resonance imaging</topic><topic>Male</topic><topic>MicroRNAs</topic><topic>Multiple sclerosis</topic><topic>Multiple Sclerosis, Relapsing-Remitting - immunology</topic><topic>Multiple Sclerosis, Relapsing-Remitting - pathology</topic><topic>Pediatrics</topic><topic>Retrospective Studies</topic><topic>Severity of Illness Index</topic><topic>Software</topic><topic>Transcriptome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Menascu, Shay</creatorcontrib><creatorcontrib>Khavkin, Yulia</creatorcontrib><creatorcontrib>Zilkha‐Falb, Rina</creatorcontrib><creatorcontrib>Dolev, Mark</creatorcontrib><creatorcontrib>Magalashvili, David</creatorcontrib><creatorcontrib>Achiron, Anat</creatorcontrib><creatorcontrib>Gurevich, Michael</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Psychology Database (Alumni)</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>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest Psychology</collection><collection>Publicly Available Content Database</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>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Annals of clinical and translational neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Menascu, Shay</au><au>Khavkin, Yulia</au><au>Zilkha‐Falb, Rina</au><au>Dolev, Mark</au><au>Magalashvili, David</au><au>Achiron, Anat</au><au>Gurevich, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients</atitle><jtitle>Annals of clinical and translational neurology</jtitle><addtitle>Ann Clin Transl Neurol</addtitle><date>2021-01</date><risdate>2021</risdate><volume>8</volume><issue>1</issue><spage>81</spage><epage>94</epage><pages>81-94</pages><issn>2328-9503</issn><eissn>2328-9503</eissn><abstract>Objective
To determine whether pediatric‐onset multiple sclerosis (POMS) and adults‐onset multiple sclerosis (AOMS) patients are different in initial disease severity and recovery and to investigate the associations with peripheral blood mononuclear cells (PBMCs) transcriptional profiles.
Methods
Clinical and radiological severity of first and second relapses and 6‐month recovery were analyzed in 2153 multiple sclerosis (MS) patients and compared between POMS (onset at 8–18years old) and AOMS (onset at 19–40 years old) patients. PBMCs transcriptomes of 15 POMS and 15 gender‐matched AOMS patients were analyzed 6 months after the first relapse and compared to 55 age‐matched healthy controls. Differentially Expressed Genes (DEGs) with a false discovery rate ≤ 10% were evaluated using the Partek software.
Results
POMS had increased Expanded Disability Status Scale (EDSS) score at first and second relapses, higher brain gadolinium‐enhancing T1‐lesions volume at first relapse, and more complete recovery after both relapses compared to AOMS. POMS patients, who recovered completely from the first relapse, were characterized by 19 DEGs that were mainly related to suppression of antigen presentation. Six upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls. POMS patients, who showed no recovery from the first relapse, were characterized by 28 DEGs that were mainly associated with B‐cell activation. Five upstream regulators of these genes were differentially expressed between pediatric and adult healthy controls.
Interpretation
POMS patients may have more severe first and second relapses than AOMS. However, most often, POMS have better recovery that may be attributed to PBMCs age‐related transcriptional profiles associated with antigen presentation and B‐cell activation.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>33197148</pmid><doi>10.1002/acn3.51244</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1529-4876</orcidid><orcidid>https://orcid.org/0000-0002-2020-3126</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Adult Age Age of Onset Brain - pathology Child Cohort Studies Cytokines Disability Evaluation Disease Progression Female Gender Gene expression Genomics Humans Magnetic resonance imaging Male MicroRNAs Multiple sclerosis Multiple Sclerosis, Relapsing-Remitting - immunology Multiple Sclerosis, Relapsing-Remitting - pathology Pediatrics Retrospective Studies Severity of Illness Index Software Transcriptome Young Adult |
| title | Clinical and transcriptional recovery profiles in pediatric and adult multiple sclerosis patients |
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