Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.

Encephalitis is a rare and potentially fatal manifestation of herpes simplex type 1 infection. Following genome-wide genetic analyses, we identified a previously uncharacterized and very rare heterozygous variant in the E3 ubiquitin ligase WWP2, in a 14-month-old girl with herpes simplex encephalitis. The p.

SARS-CoV-2 infects epithelial cells of the blood-cerebrospinal fluid barrier rather than endothelial cells or pericytes of the blood-brain barrier.

Background: As a consequence of SARS-CoV-2 infection various neurocognitive and neuropsychiatric symptoms can appear, which may persist for several months post infection. However, cell type-specific routes of brain infection and underlying mechanisms resulting in neuroglial dysfunction are not well understood.

Methods: Here, we investigated the susceptibility of cells constituting the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus (ChP) to SARS-CoV-2 infection using human induced pluripotent stem cell (hiPSC)-derived cellular models and a ChP papilloma-derived epithelial cell line as well as ChP tissue from COVID-19 patients, respectively.

Comprehensive proteomic analysis of JC polyomavirus-infected human astrocytes and their extracellular vesicles.

Progressive multifocal leukoencephalopathy is a crimpling demyelinating disease of the central nervous system caused by JC polyomavirus (JCPyV). Much about JCPyV propagation in the brain remains obscure because of a lack of proper animal models to study the virus in the context of the disease, thus hampering efforts toward the development of new antiviral strategies. Here, having established a robust and representative model of JCPyV infection in human-induced pluripotent stem cell-derived astrocytes, we are able to fully characterize the effect of JCPyV on the biology of the cells and show that the proteomic signature observed for JCPyV-infected astrocytes is extended to extracellular vesicles (EVs).

Tau Transfer via Extracellular Vesicles Disturbs the Astrocytic Mitochondrial System.

Tauopathies are neurodegenerative disorders involving the accumulation of tau isoforms in cell subpopulations such as astrocytes. The origins of the 3R and 4R isoforms of tau that accumulate in astrocytes remain unclear. Extracellular vesicles (EVs) were isolated from primary neurons overexpressing 1N3R or 1N4R tau or from human brain extracts (progressive supranuclear palsy or Pick disease patients or controls) and characterized (electron microscopy, nanoparticle tracking analysis (NTA), proteomics).

Ocrelizumab Impairs the Phenotype and Function of Memory CD8 T Cells: A 1-Year Longitudinal Study in Patients With Multiple Sclerosis.

Background And Objective: 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.

Generation of transgene-free human induced pluripotent stem cells from erythroblasts in feeder-free conditions.

This protocol describes the generation and characterization of human induced pluripotent stem cells (hiPSCs) from erythroblasts. A key difference with classical protocols is the reprogramming of erythroblasts from a simple blood draw as opposed to fibroblasts/keratinocytes, which requires a biopsy. Moreover, working with erythroblasts ensures that no recombination of the TCR/BCR genes occurs, as opposed to T cells and whole peripheral blood mononuclear cells-based approaches.

Intrinsic blood-brain barrier dysfunction contributes to multiple sclerosis pathogenesis.

Blood-brain barrier (BBB) breakdown and immune cell infiltration into the CNS are early hallmarks of multiple sclerosis (MS). The mechanisms leading to BBB dysfunction are incompletely understood and generally thought to be a consequence of neuroinflammation. Here, we have challenged this view and asked if intrinsic alterations in the BBB of MS patients contribute to MS pathogenesis.

Differentiation of functional astrocytes from human-induced pluripotent stem cells in chemically defined media.

This protocol describes how to obtain human astrocytes from human-induced pluripotent stem cells (hiPSCs) in chemically defined media, without the use of fetal bovine serum (FBS). FBS eases the differentiation of astrocytes but also deeply alters their phenotype, as compared with their counterparts. Our protocol generates hiPSC-derived astrocytes displaying a phenotype and functions similar to human primary astrocytes, including adequate response to inflammation, neurotransmitter uptake, and trophic support to neurons.

Encephalopathies Associated With Severe COVID-19 Present Neurovascular Unit Alterations Without Evidence for Strong Neuroinflammation.

Objective: Coronavirus disease (COVID-19) has been associated with a large variety of neurologic disorders. However, the mechanisms underlying these neurologic complications remain elusive. In this study, we aimed at determining whether neurologic symptoms were caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) direct infection or by either systemic or local proinflammatory mediators.

Advancing human induced pluripotent stem cell-derived blood-brain barrier models for studying immune cell interactions.

Human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier (BBB) models established to date lack expression of key adhesion molecules involved in immune cell migration across the BBB in vivo. Here, we introduce the extended endothelial cell culture method (EECM), which differentiates hiPSC-derived endothelial progenitor cells to brain microvascular endothelial cell (BMEC)-like cells with good barrier properties and mature tight junctions. Importantly, EECM-BMEC-like cells exhibited constitutive cell surface expression of ICAM-1, ICAM-2, and E-selectin.

Human Induced Pluripotent Stem Cell-Derived Astrocytes Are Differentially Activated by Multiple Sclerosis-Associated Cytokines.

Recent studies highlighted the importance of astrocytes in neuroinflammatory diseases, interacting closely with other CNS cells but also with the immune system. However, due to the difficulty in obtaining human astrocytes, their role in these pathologies is still poorly characterized. Here, we develop a serum-free protocol to differentiate human induced pluripotent stem cells (hiPSCs) into astrocytes.

Impaired T-cell migration to the CNS under fingolimod and dimethyl fumarate.

Objective: To evaluate the long-term effects of treatments used in MS on the T-cell trafficking profile.

Methods: We enrolled 83 patients with MS under fingolimod (FTY), natalizumab (NTZ), dimethyl fumarate (DMF), or other disease-modifying treatments (DMTs). Blood was drawn before treatment onset and up to 36-48 months.

Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis.

Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion\Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested.

Glutathione S-transferase M1 gene polymorphism and susceptibility to endometriosis in a French population.

Endometriosis is a multifactorial disease with possible genetic predisposition and involvement of environmental factors in its pathogenesis. The genetic polymorphism of glutathione S-transferase M1 (GSTM1) gene, which codes for glutathione S-transferase 1, class mu foreign compound conjugating enzyme of phase II detoxification system, was studied by polymerase chain reaction from the blood spots in patients with different stages of endometriosis (n = 50) and in controls (n = 72) of French origin. A total of 86.