EBV-specific T-cell immunity: relevance for multiple sclerosis.

Genetic and environmental factors jointly determine the susceptibility to develop multiple sclerosis (MS). Improvements in the design of epidemiological studies have helped to identify consistent environmental risk associations such as the increased susceptibility for MS following Epstein-Barr virus (EBV) infection, while biological mechanisms that drive the association between EBV and MS remain incompletely understood. An increased and broadened repertoire of antibody and T-cell immune responses to EBV-encoded antigens, especially to the dominant CD4 T-cell EBV nuclear antigen 1 (EBNA1), is consistently observed in patients with MS, indicating that protective EBV-specific immune responses are deregulated in MS and potentially contribute to disease development.

Increased EBNA1-specific antibody response in primary-progressive multiple sclerosis.

Background And Objectives: The impact of viral infections on disease susceptibility and progression has predominantly been studied in patients with relapse-onset MS (RMS). Here, we determined immune responses to ubiquitous viruses in patients with primary progressive MS (PPMS).

Methods: Antibody responses to Epstein-Barr virus (EBV), specifically to the latent EBV nuclear antigen 1 and the lytic viral capsid antigen VCA, human herpesvirus 6 (HHV-6), human cytomegalovirus (HCMV), and measles virus were determined in a cohort of 68 PPMS patients with a mean follow-up of 8 years and compared with 66 healthy controls matched for sex and age.

Complement Activation Profiles Predict Clinical Outcomes in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background And Objectives: The role of the complement system in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is not completely understood, and studies exploring its potential utility for diagnosis and prognosis are lacking. We aimed to investigate the value of complement factors (CFs) as diagnostic and prognostic biomarkers in patients with MOGAD.

Methods: Multicentric retrospective cohort study including patients with MOGAD, multiple sclerosis (MS) and aquaporin-4 seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD) with available paired serum and CSF samples.

Big data and artificial intelligence applied to blood and CSF fluid biomarkers in multiple sclerosis.

Artificial intelligence (AI) has meant a turning point in data analysis, allowing predictions of unseen outcomes with precedented levels of accuracy. In multiple sclerosis (MS), a chronic inflammatory-demyelinating condition of the central nervous system with a complex pathogenesis and potentially devastating consequences, AI-based models have shown promising preliminary results, especially when using neuroimaging data as model input or predictor variables. The application of AI-based methodologies to serum/blood and CSF biomarkers has been less explored, according to the literature, despite its great potential.

MiRNA-based therapeutic potential in multiple sclerosis.

This review will briefly introduce microRNAs (miRNAs) and dissect their contribution to multiple sclerosis (MS) and its clinical outcomes. For this purpose, we provide a concise overview of the present knowledge of MS pathophysiology, biomarkers and treatment options, delving into the role of selectively expressed miRNAs in clinical forms of this disease, as measured in several biofluids such as serum, plasma or cerebrospinal fluid (CSF). Additionally, up-to-date information on current strategies applied to miRNA-based therapeutics will be provided, including miRNA restoration therapy (lentivirus expressing a specific type of miRNA and miRNA mimic) and miRNA inhibition therapy such as antisense oligonucleotides, small molecules inhibitors, locked nucleic acids (LNAs), anti-miRNAs, and antagomirs.

Cytomegalovirus immune responses are associated with lower serum NfL and disability accumulation risk at multiple sclerosis onset.

Background: Infection by cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) play a prognostic role in multiple sclerosis (MS).

Objectives: To explore whether humoral immune responses to HCMV and EBV at disease onset were associated with changes in serum and cerebrospinal fluid (CSF) levels of inflammatory and neurodegeneration biomarkers.

Methods: Ninety-eight MS patients with a median follow-up of 20 years were included in the study.

Association of Complement Factors With Disability Progression in Primary Progressive Multiple Sclerosis.

Background And Objectives: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).

Neurofilaments as biomarkers in neurological disorders - towards clinical application.

Neurofilament proteins have been validated as specific body fluid biomarkers of neuro-axonal injury. The advent of highly sensitive analytical platforms that enable reliable quantification of neurofilaments in blood samples and simplify longitudinal follow-up has paved the way for the development of neurofilaments as a biomarker in clinical practice. Potential applications include assessment of disease activity, monitoring of treatment responses, and determining prognosis in many acute and chronic neurological disorders as well as their use as an outcome measure in trials of novel therapies.

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab.

Importance: Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay.

Objective: To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment.

Design, Setting, And Participants: This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022.

Prediction of disease activity and treatment failure in relapsing-remitting MS patients initiating daily oral DMTs.

Background: Limited data exist regarding treatment response prediction to oral disease-modifying therapies (DMTs) in multiple sclerosis (MS).

Objectives: We assessed the capacity of available scoring systems to anticipate disease activity parameters in naïve relapsing-remitting MS (RRMS) patients initiating daily oral DMTs, hypothesizing that they exhibit different predictive potentials.

Methods: We conducted a retrospective study and applied the Rio Score (RS), modified Rio Score (mRS), and MAGNIMS Score 12 months after DMT initiation.

Trans-Synaptic Degeneration in the Visual Pathway in Patients With Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.

Background And Objectives: We aimed to assess the presence of retinal neurodegeneration independent of optic neuritis (ON) in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the development of trans-synaptic anterograde degeneration in these patients after ON.

Methods: Cross-sectional, retrospective study of 34 adult patients with MOGAD and 23 healthy controls (HC). Clinical, optical coherence tomography (OCT), and MRI data were collected.

Teriflunomide and Epstein-Barr virus in a Spanish multiple sclerosis cohort: antiviral activity and clinical response.

Background: Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6) have been associated with multiple sclerosis (MS). Teriflunomide is an oral disease-modifying therapy approved for treatment of relapsing forms of MS. In the preclinical Theiler's murine encephalitis virus model of MS, the drug demonstrated an increased rate of viral clearance versus the vehicle placebo.

Global and Regional Deep Learning Models for Multiple Sclerosis Stratification From MRI.

Background: The combination of anatomical MRI and deep learning-based methods such as convolutional neural networks (CNNs) is a promising strategy to build predictive models of multiple sclerosis (MS) prognosis. However, studies assessing the effect of different input strategies on model's performance are lacking.

Purpose: To compare whole-brain input sampling strategies and regional/specific-tissue strategies, which focus on a priori known relevant areas for disability accrual, to stratify MS patients based on their disability level.

Association of magnetic resonance imaging phenotypes and serum biomarker levels with treatment response and long-term disease outcomes in multiple sclerosis patients.

Background And Purpose: The aim was to evaluate whether magnetic resonance imaging (MRI) phenotypes defined by inflammation and neurodegeneration markers correlate with serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in relapsing-remitting multiple sclerosis (RRMS) patients; and to explore the role of radiological phenotypes and biomarker levels on treatment response and long-term prognostic outcomes.

Methods: Magnetic resonance imaging scans from 80 RRMS patients were classified at baseline of interferon-beta (IFNβ) treatment into radiological phenotypes defined by high and low inflammation and high and low neurodegeneration, based on the number of contrast-enhancing lesions, brain parenchymal fraction and the relative volume of non-enhancing black holes on T1-weighted images. Serum levels of NfL and GFAP were measured at baseline with single molecule array (Simoa) assays.

A single-dose strategy for immunization with live attenuated vaccines is an effective option before treatment initiation in multiple sclerosis patients.

Background: Mumps-Measles-Rubella (MMR) and Varicella zoster vaccines (VAR) are live attenuated vaccines, usually administered in a two-dose scheme at least 4 weeks apart. However, single-dose immunization schemes may also be effective and can reduce delays in immunosuppressive treatment initiation in patients with multiple sclerosis (pwMS) who need to be immunized.

Objectives: To evaluate the immunogenicity of a single-dose attempt (SDA) versus the standard immunization scheme (SIS) with VAR and/or MMR in pwMS.

Myelin Oligodendrocyte Glycoprotein Antibodies in Adults with a First Demyelinating Event Suggestive of Multiple Sclerosis.

Objective: Myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) distinguish multiple sclerosis (MS) from MOG-associated disease in most cases. However, studies analyzing MOG-Ab at the time of a first demyelinating event suggestive of MS in adults are lacking. We aimed to (1) evaluate the prevalence of MOG-Ab in a first demyelinating event suggestive of MS and (2) compare clinical and paraclinical features between seropositive (MOG-Ab+) and seronegative (MOG-Ab-) patients.

Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury.

Objectives: Neurofilament light chain (NfL) has emerged as a promising biomarker for detecting and monitoring axonal injury. Until recently, NfL could only be reliably measured in cerebrospinal fluid, but digital single molecule array (Simoa) technology has enabled its precise measurement in blood samples where it is typically 50-100 times less abundant. We report development and multi-center validation of a novel fully automated digital immunoassay for NfL in serum for informing axonal injury status.

Molecular signature associated with cladribine treatment in patients with multiple sclerosis.

Introduction: Little is known about the molecular profiling associated with the effect of cladribine in patients with multiple sclerosis (MS). Here, we aimed first to characterize the transcriptomic and proteomic profiles induced by cladribine in blood cells, and second to identify potential treatment response biomarkers to cladribine in patients with MS.

Methods: Gene, protein and microRNA (miRNA) expression profiles were determined by microarrays (genes, miRNAs) and mass spectrometry (proteins) in peripheral blood mononuclear cells (PBMCs) from MS patients after treatment with cladribine in its active and inactive forms.

Liquid Biopsy in Neurological Diseases.

The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine, and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components, such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumour cells, circulating tumour DNA, transfer RNA, and circular DNA or RNA derived from body fluids.