Identification of cellular factors associated with inflammation and neurodegeneration in multiple sclerosis.

Background: Serum biomarkers as neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) enabled early identification of multiple sclerosis (MS) patients at risk of relapse-associated worsening (RAW) or progression independent of relapses (PIRA). However, the immunological mechanisms underlying these clinical phenotypes remain unclear.

Methods: We conducted a cross-sectional study including 117 MS patients and 84 healthy controls (HC).

Severity-Dependent Neuroaxonal Damage Assessed by Serum Neurofilaments in ICANS Patients Undergoing CD19-Targeted CAR T-Cell Therapy.

Background And Objectives: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a potential complication following Chimeric Antigen Receptor (CAR) T-cell infusion. Biomarkers to aid in early diagnosis and severity assessment are lacking. We aim to describe and compare serum neurofilament light chain (sNfL) dynamics in non-Hodgkin lymphoma (NHL) patients undergoing anti-CD19 CAR T-cell therapy, based on ICANS presence and severity.

Combining CSF and Serum Biomarkers to Differentiate Mechanisms of Disability Worsening in Multiple Sclerosis.

The combined use of serum and CSF biomarkers for prognostic stratification in multiple sclerosis (MS) remains underexplored. This multicenter observational study investigated associations between serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), and CSF lipid-specific IgM oligoclonal bands (LS-OCMB) with different forms of disability worsening, such as relapse-associated worsening (RAW), active progression independent of relapse activity (aPIRA), and non-active PIRA (naPIRA). A total of 535 patients with MS were included, all sampled within one year of disease onset.

The Variant rs7665090 Is Associated With Interferon-Beta Response in Multiple Sclerosis Patients.

Background: GG homozygosity for the risk gene variant rs7665090 has been reported to enhance nuclear factor kappa B (NFκB) activity in T cells from multiple sclerosis (MS) patients. Here, we investigated the association between this polymorphism and the response to different disease-modifying therapies in MS.

Methods: The rs7665090 polymorphism was genotyped in 558 MS patients treated with injectable therapies [IFNβ (n = 213) and glatiramer acetate (n = 55)], oral therapies [dimethylfumarate (n = 97), teriflunomide (n = 41), and fingolimod (n = 37)], and natalizumab (n = 115).

Deep learning to predict progression independent of relapse activity at a first demyelinating event.

Progression independent of relapse activity is the main cause of irreversible disability in multiple sclerosis and is strongly associated with older age at symptom onset. Early and accurate prediction, at symptom onset, of which patients are at highest risk of progression independent of relapses, is an unmet need. This study aimed to develop a deep learning survival model using only routine MRI acquired at the first demyelinating attack to predict the risk of progression independent of relapses, and assess its ability to improve classical age-adjusted predictions.

Cerebrospinal 14-3-3 Protein Levels as a Neuroaxonal Biomarker in Aquaporin-4 Antibody-Positive Neuromyelitis Optica Spectrum Disorder.

Background And Objectives: To investigate whether CSF 14-3-3 protein levels discriminate aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) from myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and multiple sclerosis (MS) and the association of CSF 14-3-3 protein levels with clinical features in patients with AQP4-NMOSD.

Methods: This was a multicentric retrospective cohort study of patients with AQP4-NMOSD, MOGAD, and MS, with available CSF samples. 14-3-3 protein levels were quantified using ELISA and compared between the 3 conditions.

Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.

Background And Objectives: Biologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).

Prognostic Factors for Multiple Sclerosis Symptoms in Radiologically Isolated Syndrome.

Importance: Understanding the risk factors for symptom development will allow clinicians to stratify people with radiologically isolated syndrome (pwRIS) more effectively and tailor their management strategies accordingly.

Objective: To identify prognostic factors at radiologically isolated syndrome (RIS) diagnosis associated with the development of multiple sclerosis (MS) symptoms.

Design, Setting, And Participants: This cohort study was performed in samples collected between July 2004 and September 2022 and included 33 MS centers.

Radiologically isolated syndrome: How could we accurately diagnose a subclinical period of multiple sclerosis?

Background: Radiologically isolated syndrome (RIS) represents a subclinical period of multiple sclerosis (MS).

Objectives: We aimed to characterize and identify risk factors for developing MS in an RIS cohort and to assess various proposed RIS definitions for their predictive value in MS development.

Methods: This cohort study included all patients with at least one typical inflammatory-demyelinating lesion suggestive of MS on brain and/or spinal cord magnetic resonance imaging (MRI).

Discovery of Sphingosine-1-Phosphate Receptor Modulators as Potential CHI3L1 Inhibitors by Ligand-Based Virtual Screening and Molecular Dynamics Simulations.

Multiple sclerosis is characterized by central nervous system inflammation, demyelination, and neuronal degeneration. Current diagnostic and prognostic methods lack precision, necessitating biomarkers for personalized treatment strategies. Chitinase 3-like 1 (CHI3L1) has emerged as a potential prognostic marker, with elevated levels correlating with disease severity and relapse risk.

Personalized treatment decision algorithms for the clinical application of serum neurofilament light chain in multiple sclerosis: A modified Delphi Study.

Background: Serum neurofilament light (sNfL) chain levels, a sensitive measure of disease activity in multiple sclerosis (MS), are increasingly considered for individual therapy optimization yet without consensus on their use for clinical application.

Objective: We here propose treatment decision algorithms incorporating sNfL levels to adapt disease-modifying therapies (DMTs).

Methods: We conducted a modified Delphi study to reach consensus on algorithms using sNfL within typical clinical scenarios.

The Barcelona baseline risk score to predict long-term prognosis after a first demyelinating event: a prospective observational study.

Background: In multiple sclerosis (MS), predicting at symptom onset who will develop early and severe disability is an unmet need with significant therapeutic implications. Here we propose the Barcelona-Baseline Risk Score (BRS) model to predict long-term disease outcomes in a flexible and generalisable manner.

Methods: Using prospectively acquired data from the Barcelona first-attack cohort, we created the Barcelona-BRS model as a set of six Weibull survival models of time to an Expanded Disability Status Scale score of 3.

Short-chain fatty acids in multiple sclerosis: Associated with disability, number of T2 lesions, and inflammatory profile.

Objective: An alteration in the composition of the intestinal microbiota has been observed in patients with multiple sclerosis (pwMS) with respect to healthy controls (HC). Microorganism-derived metabolites such as short-chain fatty acids (SCFA) have been suggested to play a role in the disease. Thus, to analyze the association of SCFA with clinical and radiological parameters of the disease and with those related to the inflammatory response of the immune system.

Performance of treatment response scoring systems among patients with multiple sclerosis treated with high-efficacy therapies.

Background: Predicting treatment response and disease progression in multiple sclerosis (MS) is challenging. Treatment Response Scoring Systems (TRSS) are potentially useful, but their utility in patients receiving high-efficacy therapies and very high-efficacy therapies (HET/vHET) remains unclear.

Objective: This study aimed to evaluate the performance of TRSS in patients treated with HET/vHET.

Uncovering alternative diagnoses in patients with clinical syndromes suggestive of multiple sclerosis: A transversal study from the prospective Barcelona CIS cohort.

Background: It is essential to exclude alternative diagnoses to diagnose multiple sclerosis (MS). However, detailed descriptions of alternative diagnoses in patients with suspected MS presenting with clinically isolated syndrome (CIS) are limited.

Objectives: To describe alternative diagnoses in patients presenting with CIS suggestive of MS.

Age-Related Disability Outcomes After a First Demyelinating Event.

Background And Objectives: Emerging concepts in the early detection of multiple sclerosis (MS) progression reveal that disability accumulation can start early in the disease course. Aging in MS is increasingly recognized as a key factor for disease progression and disability accrual. We evaluate the prognostic impact of age in a cohort of patients experiencing a first demyelinating event (FDE), using a variety of disability outcomes, including some not previously assessed in age-specific studies.

Contribution of Blood Biomarkers to Multiple Sclerosis Diagnosis.

Background And Objectives: Invasive procedures may delay the diagnostic process in multiple sclerosis (MS). We investigated the added value of serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP), chitinase-3-like 1 (sCHI3L1), and the immune responses to the Epstein-Barr virus-encoded nuclear antigen 1 to current MS diagnostic criteria.

Methods: In this multicentric study, we selected patients from 2 prospective cohorts presenting a clinically isolated syndrome (CIS).

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.