4.6 Article

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

期刊

FRONTIERS IN CELLULAR NEUROSCIENCE
卷 15, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fncel.2021.705618

关键词

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

资金

  1. Sao Paulo Research Foundation (FAPESP) [2014/26431-0, 2013/00837-8, 2012/09879-2]
  2. National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM) [465489/2014-1]
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior Brazil (CAPES) [001]

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The study found that NTZ treatment significantly decreased NfL levels in CSF of MS patients, increased sHLA-G levels in serum, and enhanced tolerogenic and migratory functions of pDCs in peripheral blood.
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.

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