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Objective: c-Met, a tyrosine kinase receptor, is the unique receptor for hepatocyte growth factor (HGF). The HGF/c-Met axis is reported to modulate cell migration, maturation, cytokine production, and antigen presentation. Here, we report that CD4+c-Met+ T cells are detected at increased levels in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS).Methods: c-Met expression by CD4+ T cells was analyzed mostly by flow cytometry and by immunohistochemistry from mice and human PBMCs. The in vivo role of CD4+c-Met+ T cells was assessed in EAE.Results: CD4+c-Met+ T cells found in the CNS during EAE peak disease are characterized by a pro-inflammatory phenotype skewed towards a Th1 and Th17 polarization, with enhanced adhesion and transmigration capacities correlating with increased expression of integrin α4 (Itgα4). The adoptive transfer of Itgα4-expressing CD4+Vα3.2+c-Met+ T cells induces increased disease severity compared to CD4+Vα3.2+c-Met- T cells. Finally, CD4+c-Met+ T cells are detected in the brain of MS patients, as well as in the blood with a higher level of Itgα4. These results highlight c-Met as an immune marker of highly pathogenic pro-inflammatory and pro-migratory CD4+ T lymphocytes associated with neuroinflammation. [ABSTRACT FROM AUTHOR]

This study analyzed the cerebrospinal fluid features of 31 coronavirus disease 2019 (COVID-19) patients with neurological complications. We observed neither severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the cerebrospinal fluid, nor intrathecal immunoglobulin G (IgG) synthesis but did observe signs of blood-brain barrier disruption. These results might serve as a basis for a better understanding of SARS-CoV-2 related neuropathogenesis. [ABSTRACT FROM AUTHOR]

Objective: We aimed to determine in relapsing multiple sclerosis (MS) whether intrathecal synthesis of immunoglobulin (Ig) M and IgG is associated with outcomes reflecting inflammatory activity and chronic worsening. Methods: We compared cerebrospinal fluid analysis, clinical and magnetic resonance imaging data, and serum neurofilament light chain (sNfL) levels at baseline and follow‐up in 530 patients with relapsing MS. Patients were categorized by the presence of oligoclonal IgG bands (OCGB) and intrathecal synthesis of IgG and IgM (intrathecal fraction [IF]: IgGIF and IgMIF). Relationships with the time to first relapse, sNfL concentrations, T2‐weighted (T2w) lesions, MS Severity Score (MSSS), and time to initiation of high‐efficacy therapy were analyzed in covariate‐adjusted statistical models. Results: By categorical analysis, in patients with IgMIF the median time to first relapse was 28 months shorter and MSSS on average higher by 1.11 steps compared with patients without intrathecal immunoglobulin synthesis. Moreover, patients with IgMIF had higher sNfL concentrations, more new/enlarging T2w lesions, and higher total T2w lesion counts (all p ≤ 0.01). These associations were absent or equally smaller in patients who were positive for only OCGB or OCGB/IgGIF. Furthermore, quantitative analyses revealed that in patients with IgMIF ≥ median, the time to first relapse and to initiation of high‐efficacy therapy was shorter by 32 and by 203 months, respectively (both p < 0.01), in comparison to patients with IgMIF < median. Dose‐dependent associations were also found for IgMIF but not for IgGIF with magnetic resonance imaging‐defined disease activity and sNfL. Interpretation: This large study supports the value of intrathecal IgM synthesis as an independent biomarker of disease activity and severity in relapsing MS. ANN NEUROL 2021;90:477–489 [ABSTRACT FROM AUTHOR]

Abstract Studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, have shown that B cells markedly influence the course of the disease, although whether their effects are protective or pathological is a matter of debate. EndoS hydrolysis of the IgG glycan has profound effects on IgG effector functions, such as complement activation and Fc receptor binding, suggesting that the enzyme could be used as an immunomodulatory therapeutic agent against IgG-mediated diseases. We demonstrate here that EndoS has a protective effect in myelin oligodendrocyte glycoprotein peptide amino acid 35–55 (MOG35-55)-induced EAE, a chronic neuroinflammatory demyelinating disorder of the central nervous system (CNS) in which humoral immune responses are thought to play only a minor role. EndoS treatment in chronic MOG35-55-EAE did not impair encephalitogenic T cell priming and recruitment into the CNS of mice, consistent with a primary role of EndoS in controlling IgG effector functions. In contrast, reduced EAE severity coincided with poor serum complement activation and deposition within the spinal cord, suggesting that EndoS treatment impairs B cell effector function. These results identify EndoS as a potential therapeutic agent against antibody-mediated CNS autoimmune disorders.

Emergent measles-containing vaccination recommendation for aged 6-11 months and detection of vaccine-associated measles during a large measles outbreak in Okinawa,Japan,in 2018.Vaccine 2020; 38:2361-7. 10. Live vaccines and immunosuppressive monoclonal antibodies: weighing up the benefit-risk assessment for natalizumab. Regarding the safety concern, live vaccines are contraindicated during most courses of ISIM due to a proven or suspected risk of developing a vaccine-strain infection. But in practice, many patients who are already on ISIM treatment were never or insufficiently immunized against vaccine-preventable diseases. [Extracted from the article]

Background and purpose: Progressive multifocal leukoencephalopathy (PML) is a severe infection caused by the polyomavirus JC that develops in the central nervous system (CNS) of immunosuppressed patients. The infection frequently starts in the brain hemispheres and can spread into other CNS regions such as the brainstem. Initial isolated PML brainstem lesions are exceptional. We aimed to describe the challenging diagnosis of PML with isolated brainstem lesions at the time of disease onset. Methods: We describe a case of PML starting with an isolated brainstem lesion and reviewed clinical, radiological, and biological features of all the reported cases of isolated brainstem PML. Results: Isolated brainstem PML at disease onset is extremely rare. In addition to our case, only nine PML cases presenting with strictly isolated radioanatomical brainstem location at the time of disease onset were retrieved through the literature. All patients share similar brain magnetic resonance imaging features, without contrast enhancement. Eight patients presented with initial clinical worsening, but full recovery occurred in three patients, partial recovery in two, and death in three. Even if prognosis is reserved because of the surrounding vital structures in the brainstem, clinical recovery may occur. Conclusions: This case report and literature review emphasize that isolated brainstem lesion is an atypical presentation of PML at disease onset. [ABSTRACT FROM AUTHOR]