Contributions
Abstract: P602
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Hypothesis: Comparing the transcriptome of experimental de- and remyelinating lesions to transcriptome of MS lesions may relate gene expression to damage and repair. Quantifying proteins of these homologous genes in the CSF proteome may identify novel biomarkers.
Methods: Demyelination was induced in the corpus callosum by feeding mice with cuprizone; suspending cuprizone induced remyelination. Corpus callosum was microdissected and examined by 4x44K Agilent Whole Mouse Genome Microarray. Ingenuity pathway analysis (IPA) was used to explore pathways related to de- and remyelination. Proteomics of the CSF was examined by LC-MS/MS, and targeted quantitative proteomics of 91 individual CSF of MS patients was done by selective and parallel reaction monitoring (SRM/PRM).
Results: 644 differentially expressed genes related to de- and remyelination were identified in the corpus callosum, and were compared to transcriptome data of MS brain lesions. We have found 137 overlapping homologous genes, and examined, whether corresponding proteins are present in CSF of patients with MS. CSF of 10 controls and 10 patients with primary progressive (PP), relapsing-remitting (RRMS) and secondary progressive (SP) MS, respectively were pooled and subjected to LC-MS/MS. We could detect 20 of the 137 proteins in this CSF pool, and also explored relevant databases in order to select peptides for the additional 117 proteins. Altogether, we have screened 132 peptides of 52 proteins of the 137 homologous genes by targeted quantitative proteomics in individual CSF obtained from 30 PPMS, 27 SPMS and 41 RRMS, respectively.
Discussion: Differentially expressed genes in MS lesions can be related to pathological function by comparing transcriptome of experimental and MS lesions. Protein products of several of these genes could be detected in the proteome of CSF and quantified to identify potential biomarkers or biomarker combinations.
Disclosure: Lundbeckfonden, Scleroseforeningen, OTKA, Region of Southern Denmark, Odense University Hospital
Abstract: P602
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Hypothesis: Comparing the transcriptome of experimental de- and remyelinating lesions to transcriptome of MS lesions may relate gene expression to damage and repair. Quantifying proteins of these homologous genes in the CSF proteome may identify novel biomarkers.
Methods: Demyelination was induced in the corpus callosum by feeding mice with cuprizone; suspending cuprizone induced remyelination. Corpus callosum was microdissected and examined by 4x44K Agilent Whole Mouse Genome Microarray. Ingenuity pathway analysis (IPA) was used to explore pathways related to de- and remyelination. Proteomics of the CSF was examined by LC-MS/MS, and targeted quantitative proteomics of 91 individual CSF of MS patients was done by selective and parallel reaction monitoring (SRM/PRM).
Results: 644 differentially expressed genes related to de- and remyelination were identified in the corpus callosum, and were compared to transcriptome data of MS brain lesions. We have found 137 overlapping homologous genes, and examined, whether corresponding proteins are present in CSF of patients with MS. CSF of 10 controls and 10 patients with primary progressive (PP), relapsing-remitting (RRMS) and secondary progressive (SP) MS, respectively were pooled and subjected to LC-MS/MS. We could detect 20 of the 137 proteins in this CSF pool, and also explored relevant databases in order to select peptides for the additional 117 proteins. Altogether, we have screened 132 peptides of 52 proteins of the 137 homologous genes by targeted quantitative proteomics in individual CSF obtained from 30 PPMS, 27 SPMS and 41 RRMS, respectively.
Discussion: Differentially expressed genes in MS lesions can be related to pathological function by comparing transcriptome of experimental and MS lesions. Protein products of several of these genes could be detected in the proteome of CSF and quantified to identify potential biomarkers or biomarker combinations.
Disclosure: Lundbeckfonden, Scleroseforeningen, OTKA, Region of Southern Denmark, Odense University Hospital