NeuroImmunology

We aimed to assess the relationship between levels of a cerebrospinal fluid (CSF) marker of pericyte damage, soluble platelet-derived growth factor receptor β (sPDGFRβ) and CSF markers of blood-brain barrier (BBB) integrity (CSF albumin and CSF/serum albumin ratio) and disease pathology (reduced...

Credit: W. Jiao and Q.Zeng (EPFL) In 2018, breast cancer was the most common cancer in women worldwide, accounting...

Background There is increasing evidence that B lymphocytes are involved in the pathogenesis of multiple sclerosis, and they may be a therapeutic target. Rituximab, a monoclonal antibody, selectivel...

Multiple sclerosis is a chronic autoimmune disease of the central nervous system that results in varying degrees of disability. Progressive multiple sclerosis, characterized by a steady increase in neurological disability independently of relapses, can occur from onset (primary progressive) or...

Abstract Accumulating data on patients with autoimmune encephalitis have shed light on specificities concerning clinical presentation and outcomes, which are dependent on the antigen targeted by th...

For those of you now old enough to remember “Life on Mars”….yes it was a TV programme about a Cop who travelled back in time to the 1970s..sexism, bad haircuts, those platform sho…...

KEY POINTS DN B cells are abnormally elevated in MS patients but have the same origin as in HC. DN B cells resemble CSM B cells but appear to be at an earlier maturation state. DN and CSM B cells undergo unique differentiation pathways. Abstract IgD−CD27− double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis (MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgD−CD27+ class-switched memory (CSM) and IgD+CD27− naive B cells of HC (n = 48) and MS patients (n = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients (n = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. Phenotypic analysis indicated a mature state of DN B cells by low CD5, CD10, and CD38 expression. However, the frequency of CD95+ and IgA+ cells was lower in DN versus CSM B cells. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although >95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state. Footnotes This work was supported by the National Multiple Sclerosis Society through a grant to K.C.O. (under Award PP-1509-06370) and the Belgian Charcot Foundation. J.F. is a postdoctoral fellow of the Fund for Scientific Research, Flanders. S.H.K. and S.M. were funded in part by the National Institutes of Health (Award R01AI104739). The sequencing data presented in this article have been submitted to the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra) under BioProject accession number PRJNA429427. The online version of this article contains supplemental material. Received September 10, 2018. Accepted July 11, 2019. Copyright © 2019 by The American Association of Immunologists, Inc.

Mosquito-borne virus infections, such as West Nile and Zika, have debilitating cognitive effects that persist despite recovery from encephalitis. Garber et al. identify mechanisms by which antiviral T cell persistence after recovery from infection leads to impairments in cognition via...

In this Review, Matthews considers how advanced imaging techniques are enabling in vivo visualization of chronic CNS inflammation in multiple sclerosis that has previously been identified in histopathological studies.

The pathophysiological complexity of progressive multiple sclerosis (MS) challenges the development of effective treatments, despite the substantial unmet clinical need. In this Review, Faissner, Yong and colleagues highlight the need for therapies that target inflammation, neurodegeneration and...

Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease characterized by both inflammatory demyelination and impaired remyelination. Studies indicate that Toll-like receptor 2 (TLR2) signaling contributes to both the inflammatory component and the defective remyelination in MS.