Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination
A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (H...
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Veröffentlicht in: | Multiple sclerosis 2008-06, Vol.14 (5), p.577-594 |
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description | A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing–remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses. |
doi_str_mv | 10.1177/1352458507087468 |
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The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing–remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses.</description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1177/1352458507087468</identifier><identifier>PMID: 18566024</identifier><identifier>CODEN: MUSCFZ</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Adult ; Aged ; Autoimmunity - genetics ; Autoimmunity - immunology ; Baculoviral IAP Repeat-Containing 3 Protein ; Biological and medical sciences ; Blotting, Western ; Brain - pathology ; Brain - physiology ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Demyelinating Diseases - genetics ; Demyelinating Diseases - immunology ; Demyelinating Diseases - pathology ; Female ; Gene Expression - immunology ; Gene Expression Profiling ; Humans ; Immunologic Factors - genetics ; Immunologic Factors - immunology ; Inhibitor of Apoptosis Proteins - genetics ; Inhibitor of Apoptosis Proteins - immunology ; Inhibitor of Apoptosis Proteins - metabolism ; Male ; Medical sciences ; Microglia - immunology ; Microtubule-Associated Proteins - genetics ; Microtubule-Associated Proteins - immunology ; Microtubule-Associated Proteins - metabolism ; Middle Aged ; Multiple Sclerosis - genetics ; Multiple Sclerosis - immunology ; Multiple Sclerosis - pathology ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Neoplasm Proteins - genetics ; Neoplasm Proteins - immunology ; Neoplasm Proteins - metabolism ; Neurology ; Neuronal Apoptosis-Inhibitory Protein - genetics ; Neuronal Apoptosis-Inhibitory Protein - immunology ; Neuronal Apoptosis-Inhibitory Protein - metabolism ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Ubiquitin-Protein Ligases ; X-Linked Inhibitor of Apoptosis Protein - genetics ; X-Linked Inhibitor of Apoptosis Protein - immunology ; X-Linked Inhibitor of Apoptosis Protein - metabolism</subject><ispartof>Multiple sclerosis, 2008-06, Vol.14 (5), p.577-594</ispartof><rights>2008 INIST-CNRS</rights><rights>SAGE Publications © Jun 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c404t-c29521c6574f2c09194edd9d4d51690355cc69fca66617e33d939fde42ab952a3</citedby><cites>FETCH-LOGICAL-c404t-c29521c6574f2c09194edd9d4d51690355cc69fca66617e33d939fde42ab952a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/1352458507087468$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/1352458507087468$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20474420$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18566024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hebb, ALO</creatorcontrib><creatorcontrib>Moore, CS</creatorcontrib><creatorcontrib>Bhan, V</creatorcontrib><creatorcontrib>Campbell, T</creatorcontrib><creatorcontrib>Fisk, JD</creatorcontrib><creatorcontrib>Robertson, HA</creatorcontrib><creatorcontrib>Thorne, M</creatorcontrib><creatorcontrib>Lacasse, E</creatorcontrib><creatorcontrib>Holcik, M</creatorcontrib><creatorcontrib>Gillard, J</creatorcontrib><creatorcontrib>Crocker, SJ</creatorcontrib><creatorcontrib>Robertson, GS</creatorcontrib><title>Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description>A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing–remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses.</description><subject>Adult</subject><subject>Aged</subject><subject>Autoimmunity - genetics</subject><subject>Autoimmunity - immunology</subject><subject>Baculoviral IAP Repeat-Containing 3 Protein</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Brain - pathology</subject><subject>Brain - physiology</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Demyelinating Diseases - genetics</subject><subject>Demyelinating Diseases - immunology</subject><subject>Demyelinating Diseases - pathology</subject><subject>Female</subject><subject>Gene Expression - immunology</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>Immunologic Factors - genetics</subject><subject>Immunologic Factors - immunology</subject><subject>Inhibitor of Apoptosis Proteins - genetics</subject><subject>Inhibitor of Apoptosis Proteins - immunology</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microglia - immunology</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Microtubule-Associated Proteins - immunology</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>Middle Aged</subject><subject>Multiple Sclerosis - genetics</subject><subject>Multiple Sclerosis - immunology</subject><subject>Multiple Sclerosis - pathology</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplasm Proteins - immunology</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Neurology</subject><subject>Neuronal Apoptosis-Inhibitory Protein - genetics</subject><subject>Neuronal Apoptosis-Inhibitory Protein - immunology</subject><subject>Neuronal Apoptosis-Inhibitory Protein - metabolism</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Ubiquitin-Protein Ligases</subject><subject>X-Linked Inhibitor of Apoptosis Protein - genetics</subject><subject>X-Linked Inhibitor of Apoptosis Protein - immunology</subject><subject>X-Linked Inhibitor of Apoptosis Protein - metabolism</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkU1rFjEUhYNYbK3uXUkQ6m5qksnHZCmlVaHgRtdD3uROm5JJxiQjvv_Gn2reDywUxFVC7nNO7j0XoTeUXFKq1AfaC8bFIIgig-JyeIbOKFeqI1qR5-3eyt2ufopelvJACFGqFy_QKR2ElITxM_T7-teSoRSfIk4TrveAfbz3G19T3j2YJS01FV_wklMFH_FkZh-2jcLzGqpfAuBiA-Q9lOEnmFCwwUujY_UmYD_Pa0xzcmswzXWLc2oat2Yf77BZa9oDgGdw3lRw2MG8heCjqa2rV-hkao7w-nieo-8319-uPne3Xz99ufp421lOeO0s04JRK4XiE7NEU83BOe24E1Rq0gthrdSTNVJKqqDvne715IAzs2lK05-j9wffNuePFUodZ18shGAipLWMUjPestX_BRkZWM-GHfjuCfiQ1hzbECOjwyCZ3EPkANkWYMkwjUv2s8nbkZJxt-Px6Y6b5O3Rd920zB4Fx6U24OIImGJNmLKJ1pe_HCNccc5I47oDV8wdPDb3z4__AEtevz8</recordid><startdate>200806</startdate><enddate>200806</enddate><creator>Hebb, ALO</creator><creator>Moore, CS</creator><creator>Bhan, V</creator><creator>Campbell, T</creator><creator>Fisk, JD</creator><creator>Robertson, HA</creator><creator>Thorne, M</creator><creator>Lacasse, E</creator><creator>Holcik, M</creator><creator>Gillard, J</creator><creator>Crocker, SJ</creator><creator>Robertson, GS</creator><general>SAGE Publications</general><general>Arnold</general><general>Sage Publications Ltd</general><scope>IQODW</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>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200806</creationdate><title>Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination</title><author>Hebb, ALO ; Moore, CS ; Bhan, V ; Campbell, T ; Fisk, JD ; Robertson, HA ; Thorne, M ; Lacasse, E ; Holcik, M ; Gillard, J ; Crocker, SJ ; Robertson, GS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c404t-c29521c6574f2c09194edd9d4d51690355cc69fca66617e33d939fde42ab952a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Autoimmunity - genetics</topic><topic>Autoimmunity - immunology</topic><topic>Baculoviral IAP Repeat-Containing 3 Protein</topic><topic>Biological and medical sciences</topic><topic>Blotting, Western</topic><topic>Brain - pathology</topic><topic>Brain - physiology</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Demyelinating Diseases - genetics</topic><topic>Demyelinating Diseases - immunology</topic><topic>Demyelinating Diseases - pathology</topic><topic>Female</topic><topic>Gene Expression - immunology</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>Immunologic Factors - genetics</topic><topic>Immunologic Factors - immunology</topic><topic>Inhibitor of Apoptosis Proteins - genetics</topic><topic>Inhibitor of Apoptosis Proteins - immunology</topic><topic>Inhibitor of Apoptosis Proteins - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microglia - immunology</topic><topic>Microtubule-Associated Proteins - genetics</topic><topic>Microtubule-Associated Proteins - immunology</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>Middle Aged</topic><topic>Multiple Sclerosis - genetics</topic><topic>Multiple Sclerosis - immunology</topic><topic>Multiple Sclerosis - pathology</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplasm Proteins - immunology</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Neurology</topic><topic>Neuronal Apoptosis-Inhibitory Protein - genetics</topic><topic>Neuronal Apoptosis-Inhibitory Protein - immunology</topic><topic>Neuronal Apoptosis-Inhibitory Protein - metabolism</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Ubiquitin-Protein Ligases</topic><topic>X-Linked Inhibitor of Apoptosis Protein - genetics</topic><topic>X-Linked Inhibitor of Apoptosis Protein - immunology</topic><topic>X-Linked Inhibitor of Apoptosis Protein - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hebb, ALO</creatorcontrib><creatorcontrib>Moore, CS</creatorcontrib><creatorcontrib>Bhan, V</creatorcontrib><creatorcontrib>Campbell, T</creatorcontrib><creatorcontrib>Fisk, JD</creatorcontrib><creatorcontrib>Robertson, HA</creatorcontrib><creatorcontrib>Thorne, M</creatorcontrib><creatorcontrib>Lacasse, E</creatorcontrib><creatorcontrib>Holcik, M</creatorcontrib><creatorcontrib>Gillard, J</creatorcontrib><creatorcontrib>Crocker, SJ</creatorcontrib><creatorcontrib>Robertson, GS</creatorcontrib><collection>Pascal-Francis</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>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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>MEDLINE - Academic</collection><jtitle>Multiple sclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hebb, ALO</au><au>Moore, CS</au><au>Bhan, V</au><au>Campbell, T</au><au>Fisk, JD</au><au>Robertson, HA</au><au>Thorne, M</au><au>Lacasse, E</au><au>Holcik, M</au><au>Gillard, J</au><au>Crocker, SJ</au><au>Robertson, GS</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2008-06</date><risdate>2008</risdate><volume>14</volume><issue>5</issue><spage>577</spage><epage>594</epage><pages>577-594</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><coden>MUSCFZ</coden><abstract>A failure of autoreactive T cells to undergo apoptosis may contribute to the pathogenesis of multiple sclerosis (MS). The role of the inhibitor of apoptosis (IAP) family of anti-apoptotic proteins such as X-linked IAP (XIAP), human inhibitor of apoptosis-1 (HIAP-1), human inhibitor of apoptosis-2 (HIAP-2), neuronal apoptosis inhibitory protein (NAIP) and Survivin in relapsing–remitting, secondary-progressive, primary-progressive or benign forms of MS is unclear. We report here that expression of the IAP family of genes in peripheral blood samples and brain tissues from MS cases support a role for differential regulation of these potent anti-apoptotic proteins in the pathology of MS. XIAP mRNA and protein levels were elevated in peripheral blood mononuclear cells from patients with active disease relative to normal subjects. In patients with active MS, HIAP-1 and HIAP-2 mRNA levels were elevated in resting T cells while NAIP mRNA was increased in whole blood. In post-mortem MS brain tissue, XIAP and HIAP-1 in myelin lesions were co-localized with microglia and T cells, respectively. Only in primary-progressive patients was Survivin expression elevated suggestive of a distinct pathological basis for this subtype of MS. Taken together, these results suggest that patterns of inhibitor of apoptosis expression in immune cells may have value in distinguishing between MS subtypes and offer insight into the mechanisms responsible for their distinct clinical courses.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>18566024</pmid><doi>10.1177/1352458507087468</doi><tpages>18</tpages></addata></record> |
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subjects | Adult Aged Autoimmunity - genetics Autoimmunity - immunology Baculoviral IAP Repeat-Containing 3 Protein Biological and medical sciences Blotting, Western Brain - pathology Brain - physiology Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Demyelinating Diseases - genetics Demyelinating Diseases - immunology Demyelinating Diseases - pathology Female Gene Expression - immunology Gene Expression Profiling Humans Immunologic Factors - genetics Immunologic Factors - immunology Inhibitor of Apoptosis Proteins - genetics Inhibitor of Apoptosis Proteins - immunology Inhibitor of Apoptosis Proteins - metabolism Male Medical sciences Microglia - immunology Microtubule-Associated Proteins - genetics Microtubule-Associated Proteins - immunology Microtubule-Associated Proteins - metabolism Middle Aged Multiple Sclerosis - genetics Multiple Sclerosis - immunology Multiple Sclerosis - pathology Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Neoplasm Proteins - genetics Neoplasm Proteins - immunology Neoplasm Proteins - metabolism Neurology Neuronal Apoptosis-Inhibitory Protein - genetics Neuronal Apoptosis-Inhibitory Protein - immunology Neuronal Apoptosis-Inhibitory Protein - metabolism T-Lymphocytes - immunology T-Lymphocytes - metabolism Ubiquitin-Protein Ligases X-Linked Inhibitor of Apoptosis Protein - genetics X-Linked Inhibitor of Apoptosis Protein - immunology X-Linked Inhibitor of Apoptosis Protein - metabolism |
title | Expression of the inhibitor of apoptosis protein family in multiple sclerosis reveals a potential immunomodulatory role during autoimmune mediated demyelination |
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