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Depleting CD20 + B cells is the primary mechanism by which ocrelizumab (OCRE) is efficient in persons with multiple sclerosis (pwMS). However, the exact role of OCRE on other immune cell subsets directly or indirectly remains elusive. The purpose of this study is to characterize the dynamics of peripheral immune cells of pwMS on OCRE. We collected blood samples from 38 pwMS before OCRE onset (T0) and at 6 and 12 months (T6, T12) after initiation. To cover the immune cell diversity, using mass cytometry time of flight, we designed a 38-parameter panel to analyze B, T, and innate immune cell markers and CNS migratory markers. In parallel, viral-specific CD8 + T-cell responses were assessed by the quantification of interferon-γ secretion using the enzyme-linked immunospot assay on cytomegalovirus, Epstein-Barr virus, and influenza stimulations. Beside B-cell depletion, we observed a loss in memory CD8 + CD20 + and central memory CD8 + T cells but not in CD4 + CD20 + T cells already at T6 and T12 (p < 0.001). The loss of memory CD8 + T cells correlated with a lower CXCR3 expression (p < 0.001) and CNS-related LFA-1 integrin expression (p < 0.001) as well as a reduced antiviral cellular immune response observed at both time points (p < 0.001). Of note, we did not observe major changes in the phenotype of the other cell types studied. Seven of 38 (18.4%) patients in our cohort presented with infections while on OCRE; 4 of which were switched from dimethyl fumarate. Finally, using a mixed linear model on mass cytometry data, we demonstrated that the immunomodulation induced by previous disease-modifying therapies (DMTs) was prolonged over the period of the study. In addition to its well-known role on B cells, our data suggest that OCRE also acts on CD8 + T cells by depleting the memory compartment. These changes in CD8 + T cells may be an asset in the action of OCRE on MS course but might also contribute to explain the increased occurrence of infections in these patients. Finally, although more data are needed to confirm this observation, it suggests that clinicians should pay a special attention to an increased infection risk in pwMS switched from other DMTs to OCRE.

We report on the potential use of the intrinsic ferromagnetic rare earth nitride (REN) semiconductors as ferromagnetic electrodes in tunnelling magnetoresistance and giant magnetoresistance device structures for non-volatile memory storage devices. Non-volatile memory elements utilising magnetic materials have been an industry standard for decades. However, the typical metallic ferromagnets and dilute magnetic semiconductors used lack the ability to independently tune the magnetic and electronic properties. In this regard, the rare earth nitride series offer an ultimately tuneable group of materials. Here we have fabricated two tri-layer structures using intrinsically ferromagnetic rare earth nitride semiconductors as the ferromagnetic layers. We have demonstrated both a non-volatile magnetic tunnel junction (MTJ) and an in-plane conduction device using GdN and DyN as the ferromagnetic layers, with a maximum difference in resistive states of ∼1.2% at zero-field. GdN and DyN layers were shown to be sufficiently decoupled and individual magnetic transitions were observed for each ferromagnetic layer.

Objective:To assess whether chronic white matter inflammation in patients with multiple sclerosis (MS) as detected in vivo by paramagnetic rim MRI lesions (PRLs) is associated with higher serum neurofilament light chain (sNfL) levels, a marker of neuroaxonal damage. Methods:In 118 patients with MS with no gadolinium-enhancing lesions or recent relapses, we analyzed 3D-submillimeter phase MRI and sNfL levels. Histopathologic evaluation was performed in 25 MS lesions from 20 additional autopsy MS cases. Results:In univariable analyses, participants with ≥2 PRLs (n = 43) compared to those with ≤1 PRL (n = 75) had higher age-adjusted sNfL percentiles (median, 91 and 68;p< 0.001) and higher Multiple Sclerosis Severity Scale scores (MSSS median, 4.3 and 2.4;p= 0.003). In multivariable analyses, sNfL percentile levels were higher in PRLs ≥2 cases (βadd, 16.3; 95% confidence interval [CI], 4.6-28.0;p< 0.01), whereas disease-modifying treatment (DMT), Expanded Disability Status Scale (EDSS) score, and T2 lesion load did not affect sNfL. In a similar model, sNfL percentile levels were highest in cases with ≥4 PRLs (n = 30; βadd, 30.4; 95% CI, 15.6-45.2;p< 0.01). Subsequent multivariable analysis revealed that PRLs ≥2 cases also had higher MSSS (βadd, 1.1; 95% CI, 0.3-1.9;p< 0.01), whereas MSSS was not affected by DMT or T2 lesion load. On histopathology, both chronic active and smoldering lesions exhibited more severe acute axonal damage at the lesion edge than in the lesion center (edge vs center:p= 0.004 andp= 0.0002, respectively). Conclusion:Chronic white matter inflammation was associated with increased levels of sNfL and disease severity in nonacute MS, suggesting that PRL contribute to clinically relevant, inflammation-driven neurodegeneration.

Cholesterol is a member of the sterol family that plays essential roles in biological processes, including cell membrane stability and myelin formation. Cholesterol can be metabolized into several molecules including bile acids, hormones, and oxysterols. Studies from the last few decades have demonstrated that oxysterols are not only active metabolites but are further involved in the modulation of immune responses. Liver X Receptors (LXRs), nuclear receptors for oxysterols, are important for cholesterol homeostasis and regulation of inflammatory response but are still poorly characterized during autoimmune diseases. Here we review the current knowledge about the role of oxysterols during autoimmune conditions and focus on the implication of LXR-dependent and LXR-independent pathways. We further highlight the importance of these pathways in particular during central nervous system (CNS) autoimmunity and inflammatory bowel diseases (IBD) in both experimental models and human studies. Finally, we discuss our vision about future applications and research on oxysterols related to autoimmunity.

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Cet article propose une analyse statistique du positionnement et de la performance de la France en matière de technologies de lutte contre le réchauffement climatique. La méthodologie s'appuie sur une base de données décrivant l'ensemble des dépôts de brevets entre 1980 et 2008 dans 17 classes technologiques couvrant un large spectre de technologies liées au climat. Avec 5,2% des inventions brevetées en moyenne en 2008 dans les technologies étudiées, la France est en moyenne au 5ème rang mondial dans un classement dominé par les Etats-Unis, le Japon, la Corée du Sud et l'Allemagne. 20% des dépôts de brevet en France proviennent du secteur public, contre 10% dans les autres pays industrialisés. Plus de la moitié des inventions "climat" françaises sont protégés dans des pays étrangers, soit 1,5 fois plus que la moyenne mondiale. L'analyse par domaine technologique met en évidence un positionnement faible de la France dans les énergies renouvelables, dans lesquelles l'innovation est pourtant la plus dynamique au niveau mondial. En revanche, son positionnement est fort dans des secteurs comme le nucléaire (même si elle n'arrive qu'au troisième rang derrière le Japon et les Etats-Unis), la capture et séquestration du carbone (CSC), l'isolation, le ciment, le chauffage, l'hydraulique et les véhicules électriques et hybrides, où elle tire parti de la présence et du potentiel innovant des grandes firmes françaises d'envergure internationale (Air Liquide, Alstom, Areva, Electricité de France, Lafarge, PSA Peugeot Citroën, Renault, Saint-Gobain, Schlumberger) et des organismes publics de recherche scientifique (CNRS, Commissariat à l'Energie Atomique, Institut Français du Pétrole).

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