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

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

doi:10.3389/fncel.2021.705618

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

Front Cell Neurosci. 2021 Jul 26:15:705618. doi: 10.3389/fncel.2021.705618. eCollection 2021.

Authors

Adriel S Moraes¹, Vinicius O Boldrini¹, Alliny C Dionete¹, Marilia D Andrade¹, Ana Leda F Longhini^{1

2}, Irene Santos¹, Amanda D R Lima¹, Veronica A P G Silva¹, Rafael P C Dias Carneiro^{1

3

4}, Raphael P S Quintiliano¹, Breno B Ferrari¹, Alfredo Damasceno³, Fernando Pradella¹, Alessandro S Farias^{1

5}, Charles P Tilbery⁴, Renan B Domingues^{4

6}, Carlos Senne^{6

7}, Gustavo B P Fernandes^{6

7}, Felipe von Glehn¹, Carlos Otavio Brandão^{1

3}, Carla R A V Stella³, Leonilda M B Santos^{1

5}

Affiliations

¹ Neuroimmunology Unit, Department of Genetics, Evolution, Microbiology, and Immunology, University of Campinas (UNICAMP), Campinas, Brazil.
² Department of Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, United States.
³ Department of Neurology, University of Campinas, Campinas, Brazil.
⁴ MS Clinic of Santa Casa de São Paulo (CATEM), São Paulo, Brazil.
⁵ National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
⁶ Senne Liquor Diagnóstico, São Paulo, Brazil.
⁷ Hospital Israelita Albert Einstein, São Paulo, Brazil.

Abstract

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). However, little is known about the function of plasmacytoid cells in NTZ-treated MS patients.

Objective: To 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.

Methods: CSF NfL and serum sHLA-G levels were measured using an ELISA assay, while pDCs (BDCA-2⁺) were accessed through flow cytometry analyses.

Results: CSF 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.

Conclusion: These 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.

Keywords: HLA-DR; HLA-G; PD-L1; cerebrospinal fluid; neurofilament light chain; neuroinflammation.

Copyright © 2021 Moraes, Boldrini, Dionete, Andrade, Longhini, Santos, Lima, Silva, Dias Carneiro, Quintiliano, Ferrari, Damasceno, Pradella, Farias, Tilbery, Domingues, Senne, Fernandes, von Glehn, Brandão, Stella and Santos.