To study the association of Epstein–Barr virus (EBV) and multiple sclerosis (MS) as compared to 10 different control diseases, 10,669 patients with MS and 42,222 controls were identified by ICD10 cod...

Epstein-Barr virus reprograms autoreactive B cells as antigen-presenting cells to promote pathogenic antinuclear T and B cell responses in lupus.

This study characterizes extracellular vesicles (EVs) separated from postmortem normal-appearing white matter of multiple sclerosis (MS) and control brains. Proteomic analysis revealed downregulation...

Zaic et al. report that relapsing-remitting multiple sclerosis patients show elevated cerebrospinal fluid T and B lymphocytes compared with controls, with

BACKGROUND: TB meningitis (TBM) has up to 50% mortality in people living with HIV. We investigated differences in cerebrospinal fluid (CSF) host immune responses associated with acute mortality. METHO...

Recently, a large pool of antigens derived from viral and bacterial microorganisms showing molecular mimicry with tumour-cell-expressed antigens was identified. These antigens can be presented by MHC ...

Chronic neuroinflammation and neurodegeneration are critical but unresolved drivers of disability accumulation in progressive multiple sclerosis (MS). Chronic active white matter lesions, identifiable...

TCR-based HLA similarity network reveals hidden cross-reactivity among HLA types and its role in disease and transplantation.

Myelin damage in multiple sclerosis can be detected up to 7 years before symptoms, with early immune pathway activation and a 21-protein panel showing promise for presymptomatic diagnosis.

Myelin damage in multiple sclerosis can be detected up to 7 years before symptoms, with early immune pathway activation and a 21-protein panel showing promise for presymptomatic diagnosis.

Progressive multiple sclerosis (PMS), which is characterized by relentless disease progression, lacks effective treatment. While recent studies have h…

Introduction Sphingosine-1-phosphate receptor (S1PR) modulators are effective therapies for multiple sclerosis (MS) that block lymphocyte egress from secondary lymphoid organs. This migration inhibition carries the risk of reduced infection-control as reported for the non-selective S1PR modulator, fingolimod. CXCL13:CXCR5-associated immune activities play a key role in protective antibody-based immunity but are also linked to inflammation in MS. Utilizing the ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, we aimed to determine whether selective S1PR modulation with ozanimod acts on the CXCL13:CXCR5 axis for modulating MS activity and whether this impacts anti-viral immune responses. Methods This 1-year observational study included 20 patients with MS receiving ozanimod and 10 healthy probands. CXCR5+ T cells, B cells, serum CXCL13, anti-SARS-CoV-2 serostatus, and SARS-CoV-2-spike protein (ProtS)-reactive T cell responses were measured at 3-month intervals. Results CXCR5+ T and B cell frequencies and serum CXCL13, but not anti-SARS-CoV-2 responses, declined after ozanimod initiation. Anti-SARS-CoV-2 antibody and ProtS-reactive T cell responses peaked after recall vaccinations and break-through infections. Notably, ProtS-reactive T cell frequencies shifted from CD4+ to CD8+ T cell responses in patients treated with ozanimod compared to controls. Conclusion Selective S1P receptor modulation with ozanimod affects the CXCL13:CXCR5 axis by reducing circulating CXCR5+ lymphocytes and serum CXCL13, which may contribute to reduce meningeal inflammation in MS. Moreover, the anti-SARS-CoV-2 immune defense appeared to be preserved during treatment with SARS-CoV-2-reactive CD8+ T cells, possibly compensating the lack of CD4+ T cell responses. Our immunological data may well apply to other viral infections and underscore the favorable safety and efficacy profile of ozanimod.