Validation of semaphorin 7A and ala-β-his-dipeptidase as biomarkers associated with the conversion from clinically isolated syndrome to multiple sclerosis
Cantó Puig, Ester (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tintoré, Mar
Villar, Luisa Maria (Hospital Universitario Ramón y Cajal (Madrid))
Borràs, Eva (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Alvarez-Cermeño, José C (Hospital Universitario Ramón y Cajal (Madrid))
Chiva, Cristina (Universitat Pompeu Fabra)
Sabidó, Eduard (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Rovira, Alex (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Montalban, Xavier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Comabella, Manuel (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2014
Abstract:	In a previous proteomics study using pooled cerebrospinal fluid (CSF) samples, we proposed apolipoprotein AI, apolipoprotein AIV, vitronectin, plasminogen, semaphorin 7A, and ala-β-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. 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-β-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. CSF levels of apolipoprotein AI were increased (P = 0. 043) and levels of semaphorin 7A and ala-β-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-β-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-β-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. These results validate previous findings for semaphorin 7A and ala-β-his-dipeptidase, and suggest that these proteins play a role as CSF biomarkers associated with the conversion to CDMS in CIS patients. The online version of this article (doi:10. 1186/s12974-014-0181-8) contains supplementary material, which is available to authorized users.
Grants:	Ministerio de Ciencia e Innovación FI-09-00705
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Multiple sclerosis ; Clinically isolated syndrome ; Biomarkers ; Cerebrospinal fluid ; Conversion to MS
Published in:	Journal of neuroinflammation, Vol. 11 (november 2014) , ISSN 1742-2094

DOI: 10.1186/s12974-014-0181-8
PMID: 25391360
PMID: 25406498

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