Neurofilament Light Chain ,Chitinase-3 Like-1 Proteins and Plasmacytoid Dendritic Cells in Multiple Sclerosis
- Conditions
- Multiple Sclerosis
- Interventions
- Diagnostic Test: Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic plasmacytoid Dendritic Cells
- Registration Number
- NCT05451069
- Lead Sponsor
- Assiut University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 42
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
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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Multiple sclerosis patients Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic plasmacytoid Dendritic Cells MS patients according to 2017 Macdonald criteria Non Multiple sclerosis persons Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic plasmacytoid Dendritic Cells Control persons
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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.