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In this work we have applied these techniques to the study of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> samples of multiple sclerosis (<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>) patients (<jats:italic>n\u00a0<\/jats:italic>=\u00a09), compared with samples of non\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> individuals (<jats:italic>n\u00a0<\/jats:italic>=\u00a09) using mass\u2010spectrometry. We have used western\u2010blot and analyzed cell culture to confirm pathogenic pathways suggested by mass\u2010spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>, oxidative stress, reveal that the lipid peroxidation marker 8\u2010iso\u2010prostaglandin F2\u03b1 is increased in <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde\u2010mediated protein modifications in proteins of <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> from <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content> patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal\u2010modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation\u2010modified proteins in <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator\u2010activated receptor \u03b3 (<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b3). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against <jats:italic>in situ<\/jats:italic> produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in <jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/j.1471-4159.2012.07934.x","type":"journal-article","created":{"date-parts":[[2012,8,27]],"date-time":"2012-08-27T20:45:32Z","timestamp":1346100332000},"page":"622-634","source":"Crossref","is-referenced-by-count":85,"title":["Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism"],"prefix":"10.1111","volume":"123","author":[{"given":"Hugo","family":"Gonzalo","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine PCiTAL\u2010Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Brieva","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital Arnau de Vilanova Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Tatzber","sequence":"additional","affiliation":[{"name":"Institute of Biochemical Engineering University of Applied Sciences Technikum\u2010Wien Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariona","family":"Jov\u00e9","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine PCiTAL\u2010Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cacabelos","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine PCiTAL\u2010Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cassany\u00e9","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine PCiTAL\u2010Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Lanau\u2010Angulo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine PCiTAL\u2010Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Boada","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine PCiTAL\u2010Universitat de Lleida\u2010IRBLLEIDA Lleida Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 C. 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