Neurofilament Light Chain ,Chitinase-3 Like-1 Proteins and Plasmacytoid Dendritic Cells in Multiple Sclerosis
Study Details
Study Description
Brief Summary
Multiple sclerosis (MS) is an autoimmune neurodegenerative disease characterized by demyelination and neurodegeneration of the central nervous system (CNS) . Current diagnostic criteria and management depend on MRI, clinical status, and oligoclonal immunoglobulin g bands . These markers often fail to predict relapse, progression and therapy response .There is an increased need to identify biomarkers for clinical endpoints .
One of the hallmark features of MS is axonal damage which associated with brain and cervical atrophy.Nf levels indicate the extent of axonal damage. Neurofilaments are composed of four subunits: neurofilament light polypeptides (NfL) is the most abundant and soluble and it is highly sensitive to neurodegenerative processes .
Chitinase 3-like 1 (CHI3L1) is expressed in astrocytes in the brain tissue of MS patients . CHI3L1 plays a role as prognostic biomarker in patients with MS. CHI3L1 cerebrospinal fluid levels were associated correlated with disease activity and neurological disability.
Dendritic cells (DCs) are highly specialized antigen-presenting cells with a key role in activating and preventing CNS immune-mediated damage in MS . Dendritic cells express Human Leukocyte Antigen-antigen D Related (HLA-DR) . Plasmacytoid dendritic cells characterized by the expression of blood dendritic cells antigen-2 (BDCA-2) .Plasmacytoid dendritic cells are present in the cerebrospinal fluid (CSF), leptomeninges and demyelinating lesions of patients with MS . Plasmacytoid dendritic cells also exhibit up-regulation of chemokine (CCR7C) expression. It was demonstrated increased amounts of chemokine CCR7 in the CSF from MS patients during relapses .CCR7 controls migration and functional activity of regulatory T cells and plays an important role in the establishment of tolerance .
Tolerogenic DCs (TolDCs) present an intermediate phenotype between immature dendritic cells (iDCs) and mature dendritic cells (mDCs) regarding costimulatory molecules, a pronounced shift toward anti-inflammatory . TolDCs exhibit tolerogenic molecules such as HLA-G and CD274 [programmed death-ligand 1 (PD-L1)] either in peripheral blood or in CSF. These characteristics lead to T cell clonal anergy and T cell unresponsiveness due to Ag presentation in the presence of low co-stimulation .We aim to investigate the role of NfL,(CHI3L1) and markers of plasmacytoid dendritic cells in MS.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Multiple sclerosis patients MS patients according to 2017 Macdonald criteria |
Diagnostic Test: Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic plasmacytoid Dendritic Cells
Serum and CSF levels assay of NfL and CHI3L1 using the enzyme linked immunosorbent assay kits (ELISA).
Peripheral blood mononuclear cells (PBMC) will be obtained by Ficoll-Hypaque gradient. plasmacytoid dendritic cells will be identified in (CSF) and (PBMN) based on their selective expression of surface antigen (cluster of differentiation 303) CD303, named blood dendritic cells antigen 2 (BDCA-2).Antihuman antibodies: BDCA-2, HLA-DR , CD274 , HLA-G and CCR7 for identification of tolerogenic plasmacytoid dendritic cells using flowcytometry.
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| Non Multiple sclerosis persons Control persons |
Diagnostic Test: Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic plasmacytoid Dendritic Cells
Serum and CSF levels assay of NfL and CHI3L1 using the enzyme linked immunosorbent assay kits (ELISA).
Peripheral blood mononuclear cells (PBMC) will be obtained by Ficoll-Hypaque gradient. plasmacytoid dendritic cells will be identified in (CSF) and (PBMN) based on their selective expression of surface antigen (cluster of differentiation 303) CD303, named blood dendritic cells antigen 2 (BDCA-2).Antihuman antibodies: BDCA-2, HLA-DR , CD274 , HLA-G and CCR7 for identification of tolerogenic plasmacytoid dendritic cells using flowcytometry.
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Outcome Measures
Primary Outcome Measures
- Levels of different markers in MS diagnosis [2 years]
The changes of levels of NfL and CHI3L1 using ELISA kits and its correlation with the expression of identification markers of plasmacytoid dendritic cells and its activity (HLA-DR, BDCA-2, ,CCR7C ,HLA-G and CD274) using flowcytometry in different clinical presentations of MS in consistent with MRI findings.
Secondary Outcome Measures
- Different samples levels in MS diagnosis [2 years]
Changes of levels of NfL and CHI3L1 using ELISA kits and markers of plasmacytoid dendritic using flowcytometry between blood and CSF samples of MS diagnosis.
Eligibility Criteria
Criteria
Inclusion Criteria: 1-MS patients diagnosis 2017 McDonald criteria. 2-Patients age 20-60 years 3-All males and female patients. 3-Willingness and ability to comply with the protocol. 4-Written informed consent given by the patient before the beginning of any study-related procedure, 5-Non-MS control matched age and sex persons
Exclusion Criteria:1-patients with Intracranial space-occupying lesion. 2-Abnormal intracranial pressure due to increased CSF pressure or Arnold-Chiari malformation.
3-Anticoagulant medication, coagulopathies and uncorrected bleeding diathesis. 4-Congenital spine abnormalities. 5-Local skin infection at the puncture site. 6-Not fulfill Macdonald criteria.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Assiut University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Comabella M, Deutschmann C, Midaglia L, Schierack P, Martínez J, Roggenbuck D, Montalban X. Chitinase 3-like 1 is not a target antigen in patients with multiple sclerosis. Mult Scler. 2021 Aug;27(9):1455-1457. doi: 10.1177/1352458520980141. Epub 2020 Dec 17.
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- Longhini AL, von Glehn F, Brandão CO, de Paula RF, Pradella F, Moraes AS, Farias AS, Oliveira EC, Quispe-Cabanillas JG, Abreu CH, Damasceno A, Damasceno BP, Balashov KE, Santos LM. Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse. J Neuroinflammation. 2011 Jan 7;8(1):2. doi: 10.1186/1742-2094-8-2.
- Passeri L, Marta F, Bassi V, Gregori S. Tolerogenic Dendritic Cell-Based Approaches in Autoimmunity. Int J Mol Sci. 2021 Aug 5;22(16). pii: 8415. doi: 10.3390/ijms22168415. Review.
- Piacente F, Bottero M, Benzi A, Vigo T, Uccelli A, Bruzzone S, Ferrara G. Neuroprotective Potential of Dendritic Cells and Sirtuins in Multiple Sclerosis. Int J Mol Sci. 2022 Apr 14;23(8). pii: 4352. doi: 10.3390/ijms23084352. Review.
- Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018 Jan 11;378(2):169-180. doi: 10.1056/NEJMra1401483. Review.
- Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintoré M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21. Review.
- Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019 Dec 23;16(1):272. doi: 10.1186/s12974-019-1674-2. Review.
- Multiple Sclerosis markers