Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis
In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped ac...
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| creator | Fainardi, E Castellazzi, M Bellini, T Manfrinato, M C Baldi, E Casetta, I Paolino, E Granieri, E Dallocchio, F |
| description | In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P |
| doi_str_mv | 10.1191/135248506ms1274oa |
| format | Article |
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We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS (P<0.01) and OIND (P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND (P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical (P<0.001, <0.001 and <0.05, respectively) and MRI (P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity (P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.]]></description><identifier>ISSN: 1352-4585</identifier><identifier>EISSN: 1477-0970</identifier><identifier>DOI: 10.1191/135248506ms1274oa</identifier><identifier>PMID: 16764342</identifier><identifier>CODEN: MUSCFZ</identifier><language>eng</language><publisher>Thousand Oaks, CA: SAGE Publications</publisher><subject>Adult ; Biological and medical sciences ; Biomarkers ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Enzyme Activation ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Immunomodulators ; Magnetic Resonance Imaging ; Male ; Matrix Metalloproteinase 9 - biosynthesis ; Matrix Metalloproteinase 9 - blood ; Matrix Metalloproteinase 9 - cerebrospinal fluid ; Medical sciences ; Middle Aged ; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis ; Multiple Sclerosis, Chronic Progressive - blood ; Multiple Sclerosis, Chronic Progressive - cerebrospinal fluid ; Multiple Sclerosis, Chronic Progressive - pathology ; Multiple Sclerosis, Relapsing-Remitting - blood ; Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid ; Multiple Sclerosis, Relapsing-Remitting - pathology ; Neurology ; Pharmacology. Drug treatments ; Tissue Inhibitor of Metalloproteinase-1 - biosynthesis ; Tissue Inhibitor of Metalloproteinase-1 - blood ; Tissue Inhibitor of Metalloproteinase-1 - cerebrospinal fluid</subject><ispartof>Multiple sclerosis, 2006-06, Vol.12 (3), p.294-301</ispartof><rights>2006 INIST-CNRS</rights><rights>2006 Arnold</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c395t-a968049f152ec7da09d4f2cec0d933a9757962f5b6dc45b1267561360f5998293</citedby><cites>FETCH-LOGICAL-c395t-a968049f152ec7da09d4f2cec0d933a9757962f5b6dc45b1267561360f5998293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1191/135248506ms1274oa$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1191/135248506ms1274oa$$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=17812499$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16764342$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fainardi, E</creatorcontrib><creatorcontrib>Castellazzi, M</creatorcontrib><creatorcontrib>Bellini, T</creatorcontrib><creatorcontrib>Manfrinato, M C</creatorcontrib><creatorcontrib>Baldi, E</creatorcontrib><creatorcontrib>Casetta, I</creatorcontrib><creatorcontrib>Paolino, E</creatorcontrib><creatorcontrib>Granieri, E</creatorcontrib><creatorcontrib>Dallocchio, F</creatorcontrib><title>Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis</title><title>Multiple sclerosis</title><addtitle>Mult Scler</addtitle><description><![CDATA[In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS (P<0.01) and OIND (P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND (P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical (P<0.001, <0.001 and <0.05, respectively) and MRI (P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity (P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.]]></description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Enzyme Activation</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Humans</subject><subject>Immunomodulators</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Matrix Metalloproteinase 9 - biosynthesis</subject><subject>Matrix Metalloproteinase 9 - blood</subject><subject>Matrix Metalloproteinase 9 - cerebrospinal fluid</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</subject><subject>Multiple Sclerosis, Chronic Progressive - blood</subject><subject>Multiple Sclerosis, Chronic Progressive - cerebrospinal fluid</subject><subject>Multiple Sclerosis, Chronic Progressive - pathology</subject><subject>Multiple Sclerosis, Relapsing-Remitting - blood</subject><subject>Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid</subject><subject>Multiple Sclerosis, Relapsing-Remitting - pathology</subject><subject>Neurology</subject><subject>Pharmacology. Drug treatments</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - biosynthesis</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - blood</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - cerebrospinal fluid</subject><issn>1352-4585</issn><issn>1477-0970</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kcluFDEQhlsIRELgAbggCwkEhw6220v7iEZsUiI4wLnlcVcTB_eCyx3IU_GK1DAjjQTi5JLr-__aquqx4OdCOPFKNFqqVnMzopBWzf5OdSqUtTV3lt-lmPK10q0-qR4gXnPOrW30_epEGGtUo-Rp9WsDGbZ5xiVOPrEhrbFnfuoZQl5HluAGEv75iFPJvlxBIGzJc7-GEueJzQPzFN0AG33J8ScbofiUZkIKkCdC7diLy8tPtXvJPBKVv0HGna6PCJTf62O5pRJs8SXCVJD9iOWKjWsqcUnAMCSgJiM-rO4NPiE8Orxn1Ze3bz5v3tcXH9992Ly-qEPjdKm9My1XbhBaQrC9565XgwwQeO-axjurrTNy0FvTB6W3QhqrjWgMH7RzrXTNWfV870tzfF8BSzdGDJCSn2BesSN7stCGwKd_gdfzmmmX2EnRttoZvnMTeyjQEJhh6JYcaRO3neDd7pTdP6ckzZOD8bodoT8qDrcj4NkB8EhHGbKfQsQjZ1shldsVP99z6L_Csbv_V_4NF_O39g</recordid><startdate>200606</startdate><enddate>200606</enddate><creator>Fainardi, E</creator><creator>Castellazzi, M</creator><creator>Bellini, T</creator><creator>Manfrinato, M C</creator><creator>Baldi, E</creator><creator>Casetta, I</creator><creator>Paolino, E</creator><creator>Granieri, E</creator><creator>Dallocchio, F</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>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200606</creationdate><title>Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis</title><author>Fainardi, E ; Castellazzi, M ; Bellini, T ; Manfrinato, M C ; Baldi, E ; Casetta, I ; Paolino, E ; Granieri, E ; Dallocchio, F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c395t-a968049f152ec7da09d4f2cec0d933a9757962f5b6dc45b1267561360f5998293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Enzyme Activation</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Humans</topic><topic>Immunomodulators</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Matrix Metalloproteinase 9 - biosynthesis</topic><topic>Matrix Metalloproteinase 9 - blood</topic><topic>Matrix Metalloproteinase 9 - cerebrospinal fluid</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis</topic><topic>Multiple Sclerosis, Chronic Progressive - blood</topic><topic>Multiple Sclerosis, Chronic Progressive - cerebrospinal fluid</topic><topic>Multiple Sclerosis, Chronic Progressive - pathology</topic><topic>Multiple Sclerosis, Relapsing-Remitting - blood</topic><topic>Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid</topic><topic>Multiple Sclerosis, Relapsing-Remitting - pathology</topic><topic>Neurology</topic><topic>Pharmacology. Drug treatments</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - biosynthesis</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - blood</topic><topic>Tissue Inhibitor of Metalloproteinase-1 - cerebrospinal fluid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fainardi, E</creatorcontrib><creatorcontrib>Castellazzi, M</creatorcontrib><creatorcontrib>Bellini, T</creatorcontrib><creatorcontrib>Manfrinato, M C</creatorcontrib><creatorcontrib>Baldi, E</creatorcontrib><creatorcontrib>Casetta, I</creatorcontrib><creatorcontrib>Paolino, E</creatorcontrib><creatorcontrib>Granieri, E</creatorcontrib><creatorcontrib>Dallocchio, F</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 Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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>Fainardi, E</au><au>Castellazzi, M</au><au>Bellini, T</au><au>Manfrinato, M C</au><au>Baldi, E</au><au>Casetta, I</au><au>Paolino, E</au><au>Granieri, E</au><au>Dallocchio, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis</atitle><jtitle>Multiple sclerosis</jtitle><addtitle>Mult Scler</addtitle><date>2006-06</date><risdate>2006</risdate><volume>12</volume><issue>3</issue><spage>294</spage><epage>301</epage><pages>294-301</pages><issn>1352-4585</issn><eissn>1477-0970</eissn><coden>MUSCFZ</coden><abstract><![CDATA[In this study, we employed a sensitive activity assay system to measure cerebrospinal fluid (CSF) and serum levels of active matrix metalloproteinase-9 (MMP-9) in 37 relapsing-remitting (RR), 15 secondary progressive (SP) and nine primary progressive (PP) multiple sclerosis (MS) patients, grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. We also studied, as neurological controls, 48 patients with other inflammatory neurological disorders (OIND) and 48 with non-inflammatory neurological disorders (NIND). To assess active MMP-9/TIMP-1 circuit, CSF and serum levels of MMP-9 tissue inhibitor TIMP-1 were quantified by ELISA in the same patient population. CSF mean levels of active MMP-9, CSF active MMP-9/TIMP-1 ratios and intrathecal active MMP-9 synthesis, as indicated by specific index, were more elevated in MS than in NIND (P <0.05, <0.02 and <0.02, respectively), serum active MMP-9/TIMP-1 ratio was higher in MS (P<0.01) and OIND (P<0.02) than in NIND, and serum TIMP-1 concentrations were lower in MS than in NIND (P<0.05). More importantly, serum active MMP-9 mean levels, serum active MMP-9/TIMP-1 ratio and intrathecal production of active MMP-9 were increased in MS patients with clinical (P<0.001, <0.001 and <0.05, respectively) and MRI (P<0.001, <0.001 and <0.02, respectively) disease activity, whereas CSF mean concentrations of active MMP-9 and CSF active MMP-9/TIMP-1 ratio were enhanced only in MS patients with MRI evidence of disease activity (P<0.02 and <0.01, respectively). Altogether, these findings suggest that a shift in MMP-9/TIMP-1 balance towards proteolytic activity of MMP-9 could be relevant in MS immune dysregulation. In addition, our results indicate that CSF and serum levels of active MMP-9 may represent a potential surrogate biomarker for monitoring MS disease activity. In particular, serum active MMP-9/TIMP-1 ratio seems to be a very appropriate indicator of ongoing MS inflammation, since it is easily measurable.]]></abstract><cop>Thousand Oaks, CA</cop><pub>SAGE Publications</pub><pmid>16764342</pmid><doi>10.1191/135248506ms1274oa</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 1352-4585 |
| ispartof | Multiple sclerosis, 2006-06, Vol.12 (3), p.294-301 |
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| source | SAGE Complete A-Z List; MEDLINE |
| subjects | Adult Biological and medical sciences Biomarkers Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Enzyme Activation Enzyme-Linked Immunosorbent Assay Female Humans Immunomodulators Magnetic Resonance Imaging Male Matrix Metalloproteinase 9 - biosynthesis Matrix Metalloproteinase 9 - blood Matrix Metalloproteinase 9 - cerebrospinal fluid Medical sciences Middle Aged Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis Multiple Sclerosis, Chronic Progressive - blood Multiple Sclerosis, Chronic Progressive - cerebrospinal fluid Multiple Sclerosis, Chronic Progressive - pathology Multiple Sclerosis, Relapsing-Remitting - blood Multiple Sclerosis, Relapsing-Remitting - cerebrospinal fluid Multiple Sclerosis, Relapsing-Remitting - pathology Neurology Pharmacology. Drug treatments Tissue Inhibitor of Metalloproteinase-1 - biosynthesis Tissue Inhibitor of Metalloproteinase-1 - blood Tissue Inhibitor of Metalloproteinase-1 - cerebrospinal fluid |
| title | Cerebrospinal fluid and serum levels and intrathecal production of active matrix metalloproteinase-9 (MMP-9) as markers of disease activity in patients with multiple sclerosis |
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