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Neurofilament Light Chain ,Chitinase-3 Like-1 Proteins and Plasmacytoid Dendritic Cells in Multiple Sclerosis

NCT05451069 · Status: UNKNOWN · Type: OBSERVATIONAL · Enrollment: 42

Last updated 2022-10-12

No results posted yet for this study

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.

Conditions

Interventions

DIAGNOSTIC_TEST

Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic plasmacytoid Dendritic Cells

1. Serum and CSF levels assay of NfL and CHI3L1 using the enzyme linked immunosorbent assay kits (ELISA). 2. 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.

Sponsors & Collaborators

  • Assiut University

    lead OTHER

Eligibility

Min Age
20 Years
Max Age
60 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2022-10-01
Primary Completion
2024-07-25
Completion
2025-07-27

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05451069 on ClinicalTrials.gov