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

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.

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Plasmacytoid dendritic cells are increased in cerebrospinal fluid of untreated patients during multiple sclerosis relapse

Journal of Neuroinflammation ◽

10.1186/1742-2094-8-2 ◽

2011 ◽

Vol 8 (1) ◽

pp. 2 ◽

Cited By ~ 40

Author(s):

Ana Longhini ◽

Felipe von Glehn ◽

Carlos Brandão ◽

Rosemeire FO de Paula ◽

Fernando Pradella ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Dendritic Cells ◽

Plasmacytoid Dendritic Cells ◽

Multiple Sclerosis Relapse

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Serum Neurofilament Light Chain in NMOSD and Related Disorders: Comparison According to Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibodies Status

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217317743098 ◽

2017 ◽

Vol 3 (4) ◽

pp. 205521731774309 ◽

Cited By ~ 4

Author(s):

Mariotto S ◽

Farinazzo A ◽

Monaco S ◽

Gajofatto A ◽

Zanusso G ◽

...

Keyword(s):

Light Chain ◽

Malignant Disease ◽

Serum Levels ◽

Axonal Damage ◽

Aquaporin 4 ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Spectrum Disorders ◽

Multiple Sclerosis Patients ◽

Demyelinating Disorders

Background Neurofilament light chain (NF-L) levels reflect axonal damage in different conditions, including demyelinating disorders. Objectives We aimed to compare serum NF-L levels in patients with aquaporin-4 antibodies (AQP4-Ab), myelin oligodendrocyte antibodies (MOG-Ab) and seronegative cases with neuromyelitis optica spectrum disorders and related disorders. Methods We analysed AQP4-Ab and MOG-Ab with cell-based assay and NF-L with ultrasensitive electrochemiluminescence immunoassay. Results Median NF-L levels were increased in 25 AQP4-Ab-positive patients (59 pg/ml) as compared with 22 MOG-Ab-positive cases (25 pg/ml), 52 seronegative patients (18 pg/ml), 25 multiple sclerosis patients (12 pg/ml) and 14 healthy controls (12 pg/ml). Conclusions Increased serum levels of NF-L in patients with AQP4-Ab or MOG-Ab might reflect an ongoing axonal damage and a more malignant disease course.

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Epstein-Barr virus-specific antibody response in cerebrospinal fluid and serum of patients with multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510368051 ◽

2010 ◽

Vol 16 (7) ◽

pp. 883-887 ◽

Cited By ~ 19

Author(s):

Massimiliano Castellazzi ◽

Carmine Tamborino ◽

Alice Cani ◽

Elena Negri ◽

Eleonora Baldi ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Neurological Disorders ◽

Epstein Barr Virus ◽

Serum Levels ◽

Nuclear Antigen ◽

Enzyme Linked Immunosorbent Assay ◽

Barr Virus ◽

Epstein Barr ◽

Multiple Sclerosis Patients

Cerebrospinal fluid and serum levels and intrathecal synthesis of anti-Epstein—Barr virus (EBV) IgG were measured by enzyme-linked immunosorbent assay in 80 relapsing—remitting multiple sclerosis patients grouped according to clinical and magnetic resonance imaging (MRI) evidence of disease activity. Eighty patients with other inflammatory neurological disorders (OIND) and 80 patients with non-inflammatory neurological disorders (NIND) served as neurological controls. Cerebrospinal fluid concentrations were higher in OIND than in multiple sclerosis ( p < 0.0001) and NIND ( p < 0.01) for anti-viral-capsid-antigen (anti-VCA) IgG, in multiple sclerosis than in NIND ( p < 0.01) and in OIND than in NIND ( p < 0.05) for anti-EBV nuclear antigen-1 (EBNA-1) IgG. Serum levels were more elevated in OIND than in multiple sclerosis ( p < 0.05) and in MRI inactive than in MRI active multiple sclerosis ( p < 0.0001) for anti-VCA IgG, and in multiple sclerosis than in OIND and NIND ( p < 0.01) for anti-EBNA-1 IgG. Serum titres of anti-VCA and anti-EBNA-1 IgG were also positively ( p < 0.05) and inversely ( p < 0.001) correlated, respectively, with the Expanded Disability Status Scale. An intrathecal IgG production of anti-VCA and anti-EBNA-1 IgG, as indicated by Antibody Index, was present only in a limited number of multiple sclerosis patients and controls (range from 1.3 to 6.3%). These findings do not support a direct pathogenetic role of EBV-targeted humoral immune response in multiple sclerosis.

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Effects of Repeated Intrathecal Triamcinolone-Acetonide Application on Cerebrospinal Fluid Biomarkers of Axonal Damage and Glial Activity in Multiple Sclerosis Patients

Molecular Diagnosis & Therapy ◽

10.1007/s40291-014-0114-3 ◽

2014 ◽

Vol 18 (6) ◽

pp. 631-637 ◽

Cited By ~ 13

Author(s):

P. S. Rommer ◽

F. Kamin ◽

A. Petzold ◽

H. Tumani ◽

M. Abu-Mugheisib ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Triamcinolone Acetonide ◽

Axonal Damage ◽

Cerebrospinal Fluid Biomarkers ◽

Multiple Sclerosis Patients

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Establishment of neurofilament light chain Simoa assay in cerebrospinal fluid and blood

Bioanalysis ◽

10.4155/bio-2019-0163 ◽

2019 ◽

Vol 11 (15) ◽

pp. 1405-1418 ◽

Cited By ~ 10

Author(s):

Robert Hendricks ◽

Dana Baker ◽

Jochen Brumm ◽

Teresa Davancaze ◽

Chris Harp ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Conversion Factor ◽

Plasma Samples ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Highly Sensitive ◽

Csf Biomarker ◽

Multiple Sclerosis Patients ◽

Elisa Data

Background: Neurofilament light (NfL) chain is an established cerebrospinal fluid (CSF) biomarker for neuroaxonal injury. The highly sensitive Quanterix Simoa™ platform is evaluated for NfL measurement in both CSF and blood. There is a need to link historical ELISA data that use bovine NfL to that of Simoa using a recombinant human (rhuman) NfL standard. Results/Methodology: The Simoa NF-light® Advantage Kit was validated for CSF and qualified for serum and plasma, using both rhuman and bovine NfL calibrators. Matched CSF, serum and plasma samples from 112 multiple sclerosis patients were analyzed using both calibrators. Conclusion: In multiple sclerosis, there is a good correlation between blood and CSF NfL levels. A conversion factor of approximately 5:1 was established between bovine and rhuman NfL calibrators.

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T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis

Clinical Science ◽

10.1042/cs20140608 ◽

2015 ◽

Vol 129 (4) ◽

pp. 291-303 ◽

Cited By ~ 25

Author(s):

Gabriella Ruocco ◽

Silvia Rossi ◽

Caterina Motta ◽

Giulia Macchiarulo ◽

Francesca Barbieri ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cerebrospinal Fluid ◽

Dendritic Cells ◽

Immune Cells ◽

Plasmacytoid Dendritic Cells ◽

Interleukin 17 ◽

T Helper

We have established a novel role in multiple sclerosis for a molecule, called IL-9, produced by immune cells. IL-9 reduces inflammation, and its expression in the cerebrospinal fluid of patients inversely correlates with the severity of multiple sclerosis.

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Brain disconnectome mapping and serum neurofilament light levels in multiple sclerosis

10.1101/2021.04.21.21255887 ◽

2021 ◽

Author(s):

Henning H. Rise ◽

Synne Brune ◽

Claudia Chien ◽

Tone Berge ◽

Steffan D. Bos ◽

...

Keyword(s):

Multiple Sclerosis ◽

Single Molecule ◽

Brain Network ◽

Axonal Damage ◽

Base Line ◽

Lesion Volume ◽

Neurofilament Light Chain ◽

Random Factor ◽

Neurofilament Light ◽

Multiple Sclerosis Patients

AbstractThe pathophysiological mechanisms for classical plaque characteristics and their predictive value for clinical course and outcome in multiple sclerosis is unclear. Connectivity-based approaches incorporating the distribution and magnitude of the extended brain network aberrations caused by lesions may offer higher sensitivity for axonal damage. Using individual brain disconnectome mapping, we tested the longitudinal associations between putative brain network aberrations and levels of serum neurofilament light chain (sNfL) as a neuroaxonal injury biomarker.Multiple sclerosis patients (n = 328, mean age 42.9 years, 71 % female) were prospectively enrolled at four European multiple sclerosis centres, and reassessed after two years (n = 280). Post-processing of 3 Tesla (3T) MRI data was performed at one centre using a harmonized pipeline, and disconnectome maps were calculated using BCBtoolkit based on individual lesion maps. Global disconnectivity (GD) was defined as the average disconnectome probability in each patient’s white matter. Serum NfL concentrations were measured by single molecule array (Simoa). Robust linear mixed models (rLMM) with GD or T2-lesion volume (T2LV) as dependent variables, patient and centre as a random factor, sNfL, age, sex, timepoint for visit, diagnosis, and treatment as fixed factors were run.Robust LMM revealed significant associations between higher levels of GD and increased sNfL (t = 2.30, β = 0.03, p = 0.02), age (t = 5.01, β = 0.32, p < 5.5 × 10−7), and diagnosis progressive multiple sclerosis (PMS); t = 1.97, β = 1.06, p = 0.05), but not for sex (t = 0.78, p = 0.43), treatments (effective; t = 0.85, p = 0.39, highly-effective; t = 0.86, p = 0.39) or sNfL change between base line and two-year follow up (t = −1.65, p = 0.10). Voxel-wise analyses revealed distributed associations in cerebellar and brainstem regions.In our prospective multi-site multiple sclerosis cohort, rLMMs demonstrated that the extent of global brain disconnectivity is sensitive to a systemic biomarker of axonal damage, sNfL, in patients with multiple sclerosis. These findings provide a neuropathological correlate of advanced disconnectome mapping and provide a platform for further investigations of the functional and clinical relevance in patients with brain disorders.

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