Decreased Neurofilament L Chain Levels in Cerebrospinal Fluid and Tolerogenic Plasmacytoid Dendritic Cells in Natalizumab-Treated Multiple Sclerosis Patients – Brief Research Report

Author:

Moraes Adriel S.,Boldrini Vinicius O.,Dionete Alliny C.,Andrade Marilia D.,Longhini Ana Leda F.,Santos Irene,Lima Amanda D. R.,Silva Veronica A. P. G.,Dias Carneiro Rafael P. C.,Quintiliano Raphael P. S.,Ferrari Breno B.,Damasceno Alfredo,Pradella Fernando,Farias Alessandro S.,Tilbery Charles P.,Domingues Renan B.,Senne Carlos,Fernandes Gustavo B. P.,von Glehn Felipe,Brandão Carlos Otavio,Stella Carla R. A. V.,Santos Leonilda M. B.

Abstract

BackgroundNeurofilament Light (NfL) chain levels in both cerebrospinal fluid (CSF) and serum have been correlated with the reduction of axonal damage in multiple sclerosis (MS) patients treated with Natalizumab (NTZ). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients.ObjectiveTo evaluate CSF NfL, serum levels of soluble-HLA-G (sHLA-G), and eventual tolerogenic behavior of plasmacytoid dendritic cells (pDCs) in MS patients during NTZ treatment.MethodsCSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2+) were accessed through flow cytometry analyses.ResultsCSF levels of NfL were significantly reduced during NTZ treatment, while the serum levels of sHLA-G were increased. Moreover, NTZ treatment enhanced tolerogenic (HLA-G+, CD274+, and HLA-DR+) molecules and migratory (CCR7+) functions of pDCs in the peripheral blood.ConclusionThese findings suggest that NTZ stimulates the production of molecules with immunoregulatory function such as HLA-G and CD274 programmed death-ligand 1 (PD-L1) which may contribute to the reduction of axonal damage represented by the decrease of NfL levels in patients with MS.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Frontiers Media SA

Subject

Cellular and Molecular Neuroscience

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