Combined Neurofilament Light Chain ,Chitinase-3 Like-1 Protein Levels and Tolerogenic Plasmacytoid Dendritic Cells in Defining Disease Course in Multiple Sclerosis Patients

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.