Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

Cantó, Ester; Tintoré, Mar; Villar, Luisa Maria; Borrás, Eva; Álvarez Cermeño, Jose Carlos; Chiva, Cristina; Sabidó Aguadé, Eduard, 1981-; Rovira, Alex; Montalbán Gairín, Xavier; Comabella López, Manuel

Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis

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dc.contributor.author Cantó, Esterca
dc.contributor.author Tintoré, Marca
dc.contributor.author Villar, Luisa Mariaca
dc.contributor.author Borrás, Evaca
dc.contributor.author Álvarez Cermeño, Jose Carlosca
dc.contributor.author Chiva, Cristinaca
dc.contributor.author Sabidó Aguadé, Eduard, 1981-ca
dc.contributor.author Rovira, Alexca
dc.contributor.author Montalbán Gairín, Xavierca
dc.contributor.author Comabella López, Manuelca
dc.date.accessioned 2015-03-25T10:43:31Z
dc.date.available 2015-03-25T10:43:31Z
dc.date.issued 2014ca
dc.description.abstract Background: In a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-?-his-dipeptidase as candidate biomarkers associated with the conversion to clinically definite multiple sclerosis (CDMS) in patients with clinically isolated syndromes (CIS). Here, we aimed to validate these results in individual CSF samples using alternative techniques. Methods: In a first replication study, levels of apolipoproteins AI and AIV, vitronectin, and plasminogen were measured by ELISA in CSF and serum of 56 CIS patients (29 patients who converted to CDMS (MS converters) and 27 patients who remained with CIS during follow-up (MS non-converters)) and 26 controls with other neurological disorders. Semaphorin 7A and ala-?-his-dipeptidase levels were determined by selected reaction monitoring (SRM) in CSF of 36 patients (18 MS converters, 18 non-converters) and 20 controls. In a second replication study, apolipoprotein AI levels were measured by ELISA in CSF of 74 CIS patients (47 MS converters, 27 non-converters) and 50 individual controls, and levels of semaphorin 7A and ala-beta-his-dipeptidase were determined by SRM in 49 patients (24 MS converters, 25 non-converters) and 22 controls. Results: CSF levels of apolipoprotein AI were increased (P = 0.043) and levels of semaphorin 7A and ala-?-his-dipeptidase decreased (P = 4.4?×?10?10 and P = 0.033 respectively) in MS converters compared to non-converters. No significant differences were found in serum levels for apolipoproteins AI and AIV, vitronectin, and plasminogen. Findings with semaphorin 7A and ala-?-his-dipeptidase were also validated in the second replication study, and CSF levels for these two proteins were again decreased in MS converters versus non-converters (P = 1.2?×?10?4 for semaphorin 7A; P = 3.7?×?10?8 for ala-?-his-dipeptidase). Conversely, apolipoprotein AI findings were not replicated and CSF levels for this protein did not significantly differ between groups. Furthermore, CSF semaphorin 7A levels were negatively associated with the number of T2 lesions at baseline and one-year follow-up. Conclusions: These results validate previous findings for semaphorin 7A and ala-?-his-dipeptidase, and suggest that these proteins play a role as CSF biomarkers associated with the conversion to CDMS in CIS patients.en
dc.description.sponsorship This work was supported by a grant from the 'Fondo de Investigación Sanitaria' (FIS) (grant number PI09/00788), Ministry of Science and Innovation, Spain. EC is supported by a contract from the FIS (contract number FI 09/00705), Ministry of Science and Innovation, Spainen
dc.format.mimetype application/pdfca
dc.identifier.citation Cantó E, Tintoré M, Villar LM, Borrás E, Alvarez-Cermeño JC, Chiva C, Sabidó E, Rovira A, Montalban X, Comabella M. Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis. Journal of Neuroinflammation. 2014; 11: 181. DOI 10.1186/s12974-014-0181-8ca
dc.identifier.doi http://dx.doi.org/10.1186/s12974-014-0181-8
dc.identifier.issn 1742-2094ca
dc.identifier.uri http://hdl.handle.net/10230/23273
dc.language.iso engca
dc.publisher BioMed Centralca
dc.relation.ispartof Journal of Neuroinflammation. 2014; 11: 181
dc.rights © 2014 Cantó et al., licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.ca
dc.rights.accessRights info:eu-repo/semantics/openAccessca
dc.rights.uri http://creativecommons.org/licenses/by/4.0
dc.subject.keyword Multiple sclerosisen
dc.subject.keyword Clinically isolated syndromeen
dc.subject.keyword Biomarkersen
dc.subject.keyword Cerebrospinal fluiden
dc.subject.keyword Conversion to MSen
dc.subject.other Esclerosi múltipleca
dc.title Validation of semaphorin 7A and ala-beta-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosisen
dc.type info:eu-repo/semantics/articleca
dc.type.version info:eu-repo/semantics/publishedVersionca

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