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Published on: November 29, 2019
CSF SERPINA3 Levels Are Elevated in Patients With Progressive MS.
Nicolás Fissolo1, Clara Matute-Blanch1, Mohamoud Osman1
1From the Servei de Neurologia-Neuroimmunologia (N.F., C.M.-B., C.C., R.P., V.B., X.M., M.C.L.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain; Biotech Research and Innovation Centre (BRIC) (M.O., S.I.-N.), University of Copenhagen, Denmark; Statistics and Bioinformatics Unit (B.M., A.S.), Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain; Genetics, Microbiology and Statistics Department (A.S.), Universitat de Barcelona, Spain; Department of Neurology (I.D.), University of Belgrade School of Medicine, Serbia; Department of Neurology (I.D.), University of North Carolina School of Medicine, Chapel Hill; Department of Neurology (M.V., M.K.), Medical University of Graz, Austria; Proteomics Unit (E.B., E.S.), Centre de Regulació Genòmica (CRG), Barcelona Institute of Science and Technology (BIST), Spain; Proteomics Unit (E.B., E.S.), Universitat Pompeu Fabra, Barcelona, Spain; and Center for Multiple Sclerosis (X.M.), St. Michael's Hospital, University of Toronto, ON, Canada.
Researchers identified SERPINA3 as a potential biomarker for progressive multiple sclerosis (MS). Elevated levels in cerebrospinal fluid correlate with disease progression, especially in primary progressive MS (PPMS).
Area of Science:
- Neuroscience
- Immunology
- Biomarker Discovery
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system.
- Identifying biomarkers for progressive MS phases is crucial for understanding disease mechanisms and developing targeted therapies.
- Neuroprotective strategies require biomarkers that indicate disease progression and potential therapeutic targets.
Purpose of the Study:
- To identify biomarkers associated with the progressive phases of Multiple Sclerosis (MS).
- To discover biomarkers with potential neuroprotective properties.
- To validate these biomarkers in patient cerebrospinal fluid (CSF).
Main Methods:
- Combined analysis of transcriptional and proteomic profiles from experimental autoimmune encephalomyelitis (EAE) models and neural stem cell differentiation.
- Candidate biomarkers Serpina3n and S100A4 were identified through integrative analysis.
- Cerebrospinal fluid (CSF) levels of human orthologs SERPINA3 and S100A4 were measured using ELISA in 65 MS patients and 30 controls.
Main Results:
- SERPINA3 and S100A4 were upregulated in chronic progressive EAE and induced during neuronal differentiation.
- CSF levels of SERPINA3 and S100A4 were significantly higher in MS patients compared to non-inflammatory neurologic controls (NINCs).
- CSF SERPINA3 levels were notably elevated in progressive MS forms, particularly primary progressive MS (PPMS), and correlated with neurofilament light chain in PPMS.
Conclusions:
- SERPINA3 serves as a promising biomarker for the progressive forms of MS, especially PPMS.
- The findings suggest a role for SERPINA3 in the neurodegenerative processes of MS.
- Further research into SERPINA3's neuroprotective potential and therapeutic applications is warranted.
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