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Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires
Background The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS). Methods CSF and serum samples from CIS, MS and other neurological non-MS disease were...
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Published in: | Journal of neurology 2019-01, Vol.266 (1), p.112-118 |
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container_title | Journal of neurology |
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description | Background
The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS).
Methods
CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients’ diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up.
Results
In the MS group (
n
= 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L,
p
= 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L
p
= 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (
r
= 0.72 and
r
= 0.65, respectively).
Conclusion
KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters. |
doi_str_mv | 10.1007/s00415-018-9106-2 |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2129531846</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2127843862</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-4144616b6f2c269c71a162bafafb15757a127a03d2afdc4439947aa23b939b903</originalsourceid><addsrcrecordid>eNp1kc2KFDEUhYMoTjv6AG4k4MZNaf6qUuVubJwZYcCFP9twK0l1Z0glbZIS-mV8VlN0O4IgBEK43zn33hyEXlLylhIi32VCBG0bQvtmoKRr2CO0oYKzhop2eIw2hAvStLwVF-hZzveEkL4WnqILTnjf9VJu0K_v4J2B4mLAccLbL9d4StZi73b7gvUeXMD1GAe7ELPLGILBhxTPryqZF1_cwVuctbfpgdHeBafB-yN2OXoo1uB8DCbF2b5fHfLB6uJ-WqzjPqaCc1nMce31YbHVHF-5ZPNz9GQCn-2L832Jvl1__Lq9be4-33zaXt01mktWGkGF6Gg3dhPTrBu0pEA7NsIE00hb2UqgTALhhsFktBB8GIQEYHwc-DAOhF-iNyffOtiPxeaiZpe19R6CjUtWjLKh5bQXXUVf_4PexyWFOt1KyV7Ur2WVoidK101zspM6JDdDOipK1BqeOoWnanhqDU-tmldn52WcrXlQ_EmrAuwE5FoKO5v-tv6_62_mP6Z2</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2127843862</pqid></control><display><type>article</type><title>Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires</title><source>Springer Nature</source><creator>Sáez, María Soledad ; Rojas, Juan Ignacio ; Lorenzón, María Victoria ; Sánchez, Francisco ; Patrucco, Liliana ; Míguez, Jimena ; Azcona, Carolina ; Sorroche, Patricia ; Cristiano, Edgardo</creator><creatorcontrib>Sáez, María Soledad ; Rojas, Juan Ignacio ; Lorenzón, María Victoria ; Sánchez, Francisco ; Patrucco, Liliana ; Míguez, Jimena ; Azcona, Carolina ; Sorroche, Patricia ; Cristiano, Edgardo</creatorcontrib><description>Background
The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS).
Methods
CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients’ diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up.
Results
In the MS group (
n
= 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L,
p
= 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L
p
= 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (
r
= 0.72 and
r
= 0.65, respectively).
Conclusion
KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.</description><identifier>ISSN: 0340-5354</identifier><identifier>EISSN: 1432-1459</identifier><identifier>DOI: 10.1007/s00415-018-9106-2</identifier><identifier>PMID: 30386877</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Biomarkers - blood ; Biomarkers - cerebrospinal fluid ; Cerebrospinal fluid ; Cohort analysis ; Demyelinating Diseases - blood ; Demyelinating Diseases - cerebrospinal fluid ; Diagnosis ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin kappa-Chains - blood ; Immunoglobulin kappa-Chains - cerebrospinal fluid ; Immunoglobulin lambda-Chains - blood ; Immunoglobulin lambda-Chains - cerebrospinal fluid ; Light chains ; Male ; Medicine ; Medicine & Public Health ; Multiple sclerosis ; Neurology ; Neuroradiology ; Neurosciences ; Original Communication ; Prognosis ; Prospective Studies ; Sensitivity and Specificity</subject><ispartof>Journal of neurology, 2019-01, Vol.266 (1), p.112-118</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2018</rights><rights>Journal of Neurology is a copyright of Springer, (2018). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-4144616b6f2c269c71a162bafafb15757a127a03d2afdc4439947aa23b939b903</citedby><cites>FETCH-LOGICAL-c372t-4144616b6f2c269c71a162bafafb15757a127a03d2afdc4439947aa23b939b903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30386877$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sáez, María Soledad</creatorcontrib><creatorcontrib>Rojas, Juan Ignacio</creatorcontrib><creatorcontrib>Lorenzón, María Victoria</creatorcontrib><creatorcontrib>Sánchez, Francisco</creatorcontrib><creatorcontrib>Patrucco, Liliana</creatorcontrib><creatorcontrib>Míguez, Jimena</creatorcontrib><creatorcontrib>Azcona, Carolina</creatorcontrib><creatorcontrib>Sorroche, Patricia</creatorcontrib><creatorcontrib>Cristiano, Edgardo</creatorcontrib><title>Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires</title><title>Journal of neurology</title><addtitle>J Neurol</addtitle><addtitle>J Neurol</addtitle><description>Background
The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS).
Methods
CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients’ diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up.
Results
In the MS group (
n
= 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L,
p
= 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L
p
= 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (
r
= 0.72 and
r
= 0.65, respectively).
Conclusion
KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.</description><subject>Adult</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - cerebrospinal fluid</subject><subject>Cerebrospinal fluid</subject><subject>Cohort analysis</subject><subject>Demyelinating Diseases - blood</subject><subject>Demyelinating Diseases - cerebrospinal fluid</subject><subject>Diagnosis</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Humans</subject><subject>Immunoglobulin kappa-Chains - blood</subject><subject>Immunoglobulin kappa-Chains - cerebrospinal fluid</subject><subject>Immunoglobulin lambda-Chains - blood</subject><subject>Immunoglobulin lambda-Chains - cerebrospinal fluid</subject><subject>Light chains</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Multiple sclerosis</subject><subject>Neurology</subject><subject>Neuroradiology</subject><subject>Neurosciences</subject><subject>Original Communication</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>Sensitivity and Specificity</subject><issn>0340-5354</issn><issn>1432-1459</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kc2KFDEUhYMoTjv6AG4k4MZNaf6qUuVubJwZYcCFP9twK0l1Z0glbZIS-mV8VlN0O4IgBEK43zn33hyEXlLylhIi32VCBG0bQvtmoKRr2CO0oYKzhop2eIw2hAvStLwVF-hZzveEkL4WnqILTnjf9VJu0K_v4J2B4mLAccLbL9d4StZi73b7gvUeXMD1GAe7ELPLGILBhxTPryqZF1_cwVuctbfpgdHeBafB-yN2OXoo1uB8DCbF2b5fHfLB6uJ-WqzjPqaCc1nMce31YbHVHF-5ZPNz9GQCn-2L832Jvl1__Lq9be4-33zaXt01mktWGkGF6Gg3dhPTrBu0pEA7NsIE00hb2UqgTALhhsFktBB8GIQEYHwc-DAOhF-iNyffOtiPxeaiZpe19R6CjUtWjLKh5bQXXUVf_4PexyWFOt1KyV7Ur2WVoidK101zspM6JDdDOipK1BqeOoWnanhqDU-tmldn52WcrXlQ_EmrAuwE5FoKO5v-tv6_62_mP6Z2</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Sáez, María Soledad</creator><creator>Rojas, Juan Ignacio</creator><creator>Lorenzón, María Victoria</creator><creator>Sánchez, Francisco</creator><creator>Patrucco, Liliana</creator><creator>Míguez, Jimena</creator><creator>Azcona, Carolina</creator><creator>Sorroche, Patricia</creator><creator>Cristiano, Edgardo</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</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>20190101</creationdate><title>Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires</title><author>Sáez, María Soledad ; Rojas, Juan Ignacio ; Lorenzón, María Victoria ; Sánchez, Francisco ; Patrucco, Liliana ; Míguez, Jimena ; Azcona, Carolina ; Sorroche, Patricia ; Cristiano, Edgardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-4144616b6f2c269c71a162bafafb15757a127a03d2afdc4439947aa23b939b903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Biomarkers - blood</topic><topic>Biomarkers - cerebrospinal fluid</topic><topic>Cerebrospinal fluid</topic><topic>Cohort analysis</topic><topic>Demyelinating Diseases - blood</topic><topic>Demyelinating Diseases - cerebrospinal fluid</topic><topic>Diagnosis</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Humans</topic><topic>Immunoglobulin kappa-Chains - blood</topic><topic>Immunoglobulin kappa-Chains - cerebrospinal fluid</topic><topic>Immunoglobulin lambda-Chains - blood</topic><topic>Immunoglobulin lambda-Chains - cerebrospinal fluid</topic><topic>Light chains</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Multiple sclerosis</topic><topic>Neurology</topic><topic>Neuroradiology</topic><topic>Neurosciences</topic><topic>Original Communication</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sáez, María Soledad</creatorcontrib><creatorcontrib>Rojas, Juan Ignacio</creatorcontrib><creatorcontrib>Lorenzón, María Victoria</creatorcontrib><creatorcontrib>Sánchez, Francisco</creatorcontrib><creatorcontrib>Patrucco, Liliana</creatorcontrib><creatorcontrib>Míguez, Jimena</creatorcontrib><creatorcontrib>Azcona, Carolina</creatorcontrib><creatorcontrib>Sorroche, Patricia</creatorcontrib><creatorcontrib>Cristiano, Edgardo</creatorcontrib><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>Neurosciences Abstracts</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma 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)</collection><collection>ProQuest Central UK/Ireland</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</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>Journal of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sáez, María Soledad</au><au>Rojas, Juan Ignacio</au><au>Lorenzón, María Victoria</au><au>Sánchez, Francisco</au><au>Patrucco, Liliana</au><au>Míguez, Jimena</au><au>Azcona, Carolina</au><au>Sorroche, Patricia</au><au>Cristiano, Edgardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires</atitle><jtitle>Journal of neurology</jtitle><stitle>J Neurol</stitle><addtitle>J Neurol</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>266</volume><issue>1</issue><spage>112</spage><epage>118</epage><pages>112-118</pages><issn>0340-5354</issn><eissn>1432-1459</eissn><abstract>Background
The objective was to evaluate the precision of kappa and lambda free light chains (KFLC and LFLC) in CSF for the diagnosis of multiple sclerosis (MS) and prognosis of clinically isolated syndrome (CIS).
Methods
CSF and serum samples from CIS, MS and other neurological non-MS disease were collected between 2015 and 2017. FLC concentrations were measured using immunoassay Freelite™. Results were correlated with the patients’ diagnoses and ROC curve analysis was used to determine accuracy. In CIS patients, analysis of FLC were compared in CIS converters vs. non-converter during follow-up.
Results
In the MS group (
n
= 41), the optimal cut-off for KFLC determined was 7 mg/L, with a diagnostic sensitivity and specificity of 95% and 97%, respectively. The optimal cut-off for LFLC was 0.7 mg/L, with a diagnostic sensitivity and specificity of 71% and 81%, respectively. 36 CIS patients were included; mean follow-up time was 28 ± 9 months, and 22 (61.1%) patients converted to MS. The median concentration of CSF K and LFLCs at CIS diagnosis was slightly higher in CIS-converters compared to non-converters, but this did not reach statistical significance (KFLC: median 7 ± 5.3 mg/L vs. 5 ± 2.3 mg/L,
p
= 0.11; LFLC 0.7 ± 0.33 mg/L vs. 0.5 ± 0.23 mg/L
p
= 0.16). A strong correlation was observed between the concentration of K and L FLCs at diagnosis and the change in PBVC during follow-up (
r
= 0.72 and
r
= 0.65, respectively).
Conclusion
KFLCs have a high sensitivity and specificity for the diagnosis of MS. FLC concentrations at CIS diagnosis were not significantly higher in CIS-converters.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>30386877</pmid><doi>10.1007/s00415-018-9106-2</doi><tpages>7</tpages></addata></record> |
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source | Springer Nature |
subjects | Adult Biomarkers - blood Biomarkers - cerebrospinal fluid Cerebrospinal fluid Cohort analysis Demyelinating Diseases - blood Demyelinating Diseases - cerebrospinal fluid Diagnosis Female Follow-Up Studies Humans Immunoglobulin kappa-Chains - blood Immunoglobulin kappa-Chains - cerebrospinal fluid Immunoglobulin lambda-Chains - blood Immunoglobulin lambda-Chains - cerebrospinal fluid Light chains Male Medicine Medicine & Public Health Multiple sclerosis Neurology Neuroradiology Neurosciences Original Communication Prognosis Prospective Studies Sensitivity and Specificity |
title | Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires |
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