A new myelin protein, TPPP/p25, reduced in demyelinated lesions is enriched in cerebrospinal fluid of multiple sclerosis |
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Authors: | Vincze Orsolya Oláh Judit Zádori Dénes Klivényi Péter Vécsei László Ovádi Judit |
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Affiliation: | aInstitute of Enzymology, Biological Research Center, Hungarian Academy of Sciences, Budapest, Hungary;bDepartment of Neurology, University of Szeged, Szeged, Hungary |
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Abstract: | Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease with variable extent of remyelination coupled with the differentiation of oligodendrocytes, in which Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) plays a crucial role. Previously we reported that the loss of TPPP/p25-positive oligodendrocytes in demyelinated lesions in the brain of MS patients could be a biomarker for MS [2]. In this work we tested the occurrence of TPPP/p25 in the cerebrospinal fluid (CSF) of MS patients, and by elaborating a sensitive assay for quantification of TPPP/p25 we showed that its level is significantly higher than in the case of non-MS patients. Patients with MS were diagnosed at the Department of Neurology, University of Szeged according to the clinical and laboratory diagnostic criteria of McDonald. In non-MS patients no significant pathological changes were detected on magnetic resonance imaging scans, while in MS patients multiple hyperintense T2 lesions in the white matter were detected. Kurtzke Expanded Disability Status Scale scores as well as IgG level and oligoclonal bands of MS patients were demonstrated. The sensitive assay elaborated in this study is based upon Western blot followed by chemiluminescent detection validated by human recombinant protein. The median TPPP/p25 contents in the CSF were 62.8 and 64.7 μg/L for patients with clinically isolated syndromes and relapsing remitting MS, respectively, while this value for non-MS patients was 27.9 μg/L. The enrichment of TPPP/p25 was independent of age, gender and the time period between lumbar puncture and relapse/shub. These data suggest that the TPPP/p25-based assay could be a powerful diagnostic test for MS patients. |
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Keywords: | Abbreviations: CSF, cerebrospinal fluid EDSS, Kurtzke Expanded Disability Status Scale MRI, magnetic resonance imaging MS, multiple sclerosis CIS MS, MS with clinically isolated syndromes MBP, myelin basic protein OCB, oligoclonal band OD, other disease OIND, other inflammatory neurological disease OLG, oligodendrocyte OND, other neurological disease RR MS, relapsing&ndash remitting MS TPPP/p25, Tubulin Polymerization Promoting Protein/p25 |
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