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.

Highlights

  • Natalizumab (NTZ) is one of the most effective therapy for relapsing-remitting multiple sclerosis (RRMS)

  • Its most known mechanism of action is the blockage of α4-integrins (CD49d), preventing the entry of autoreactive T- and B- lymphocytes in the central nervous system (CNS) (Bielekova and Becker, 2010)

  • At the same time, reduced CNS inflammatory activity associated with lower levels of neurofilament light chain (NfL) in the cerebrospinal fluid (CSF) has been described during NTZ treatment (Gunnarsson et al, 2011; Romme Christensen et al, 2014)

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Summary

Background

Neurofilament 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). Little is known about the function of plasmacytoid cells in NTZ-treated MS patients

Results
Conclusion
INTRODUCTION
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RESULTS AND DISCUSSION
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