Quantitative proteomic analysis of cerebrospinal fluid of women newly diagnosed with multiple sclerosis
| Autor: | Miluse Pavelcova, Jiri Petrak, Michaela Svrdlikova, Eva Havrdova, Karel Holada, Denisa Lipcseyova, Eliska Jankovska |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Proteomics
0301 basic medicine Pathology medicine.medical_specialty Multiple Sclerosis Proteome Newly diagnosed 03 medical and health sciences Multiple Sclerosis Relapsing-Remitting 0302 clinical medicine Cerebrospinal fluid medicine Humans Cerebrospinal Fluid business.industry General Neuroscience Multiple sclerosis Cerebrospinal Fluid Proteins General Medicine medicine.disease Patient diagnosis 030104 developmental biology Female business Biomarkers 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Neuroscience. 132:724-734 |
| ISSN: | 1543-5245 0020-7454 |
| DOI: | 10.1080/00207454.2020.1837801 |
| Popis: | The lack of reliable diagnostic and/or prognostic biomarkers for multiple sclerosis (MS) is the major obstacle to timely and accurate patient diagnosis in MS patients. To identify new proteins associated with MS we performed a detailed proteomic analysis of cerebrospinal fluid (CSF) of patients newly diagnosed with relapsing-remitting MS (RRMS) and healthy controls. Reflecting significantly higher prevalence of MS in women we included only women patients and controls in the study. To eliminate a potential effect of therapy on the CSF composition, only the therapy-naïve patients were included. Pooled CSF samples were processed in a technical duplicate, and labeled with stable-isotope coded TMT tags. To maximize the proteome coverage, peptide fractionation using 2D-LC preceded mass analysis using Orbitrap Fusion Tribrid Mass Spectrometer. Differential concentration of selected identified proteins between patients and controls was verified using specific antibodies. Of the identified 900 CSF proteins, we found 69 proteins to be differentially abundant between patients and controls. In addition to several proteins identified as differentially abundant in MS patients previously, we observed several linked to MS for the first time, namely eosinophil-derived neurotoxin and Nogo receptor. Our data confirm differential abundance of several previously proposed protein markers, and provide indirect support for involvement of copper–iron disbalance in MS. Most importantly, we identified two new differentially abundant CSF proteins that seem to be directly connected with myelin loss and axonal damage via TLR2 signaling and Nogo-receptor pathway in women newly diagnosed with RRMS. |
| Databáze: | OpenAIRE |
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