Neurofilament light in serum: Reference values and effect of risk factors for multiple sclerosis.

Background: The measurement of neurofilament light (NFL) in blood samples has been established as a sensitive measure of neuroaxonal damage in a wide range of diseases in the peripheral and central nervous system, including multiple sclerosis (MS). Previous studies have identified confounding factors that may influence the serum concentration of NFL.

Aim: We aimed at investigating the relationship between known confounders (age, body mass index, blood volume) and risk factors for MS (smoking and human leukocyte antigen (HLA)) on serum concentrations of NFL in control subjects.

Age-corrected neurofilament light chain ratio decreases but does not predict relapse in highly active multiple sclerosis patients initiating natalizumab treatment.

Background: Neurofilament light chain (NFL) is a biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). However, while most agree that NFL levels predict disease activity and worsening, the predictive value of NFL on future relapse risk remains uncertain.

Objective: The primary aim was to evaluate the predictive value of age-corrected serum NFL (sNFL) ratio on relapse risk in highly active relapsing-remitting MS patients (RRMS) treated with natalizumab.

The peripheral endocannabinoid system and its association with biomarkers of inflammation in untreated patients with multiple sclerosis.

Background And Purpose: The endocannabinoid system (ECS) has been found altered in patients with multiple sclerosis (MS). However, whether the ECS alteration is present in the early stage of MS remains unknown. First, we aimed to compare the ECS profile between newly diagnosed MS patients and healthy controls (HCs).

The gut microbiota in multiple sclerosis varies with disease activity.

Background: Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known.

MRI of the Entire Spinal Cord-Worth the While or Waste of Time? A Retrospective Study of 74 Patients with Multiple Sclerosis.

Spinal cord lesions are included in the diagnosis of multiple sclerosis (MS), yet spinal cord MRI is not mandatory for diagnosis according to the latest revisions of the McDonald Criteria. We investigated the distribution of spinal cord lesions in MS patients and examined how it influences the fulfillment of the 2017 McDonald Criteria. Seventy-four patients with relapsing-remitting MS were examined with brain and entire spinal cord MRI.

Methylation and Gene Expression in Relation to the Multiple Sclerosis-Associated Gene Variant rs2104286 and Soluble IL-2Rα in CD8 T Cells.

CD8 T cells are involved in the pathogenesis of multiple sclerosis (MS). The interleukin-2 receptor α (IL-2Rα) is important for CD8 T cell function, and single nucleotide polymorphisms (SNPs) in the gene encoding IL-2Rα increase the risk of MS. Therefore, in isolated CD8 T cells we investigated gene methylation and gene expression in relation to the MS-associated SNP rs2104286 and soluble IL-2Rα (sIL-2Rα).

Biomarkers of systemic inflammation, soluble IL-2Rα and the multiple sclerosis-associated IL2RA SNP rs2104286 in healthy subjects and multiple sclerosis patients.

Soluble interleukin-2 (IL-2) receptor α (sIL-2Rα) antagonizes IL-2 signaling and is involved in the pathogenesis of several immune-mediated diseases including multiple sclerosis (MS). The level of sIL-2Rα is affected by the MS-associated single nucleotide polymorphism (SNP) rs2104286. By use of ELISA and electrochemiluminescence, we investigated if 26 biomarkers of systemic inflammation were associated with sIL-2Rα and rs2104286 in cohorts of healthy subjects and MS patients in serum and heparin plasma.

Serum Short-Chain Fatty Acids and Associations With Inflammation in Newly Diagnosed Patients With Multiple Sclerosis and Healthy Controls.

Multiple sclerosis (MS) is a chronic immune-mediated disease characterized by demyelination and neuroaxonal damage in the central nervous system. The etiology is complex and is still not fully understood. Accumulating evidence suggests that our gut microbiota and its metabolites influence the MS pathogenesis.

Pregnancy-Induced Changes in microRNA Expression in Multiple Sclerosis.

Pregnancy affects the disease course in multiple sclerosis (MS), particularly in the third trimester, where the relapse rate is reduced by as much as two thirds. This study aimed at identifying changes in microRNA (miRNA) and immune cell phenotypes in pregnant MS patients. Discovery and validation studies to detect differentially expressed miRNAs were performed with quantitative real-time PCR on peripheral blood mononuclear cells (PBMC).

A novel neurodegenerative spectrum disorder in patients with MLKL deficiency.

Mixed lineage kinase domain-like (MLKL) is the main executor of necroptosis, an inflammatory form of programmed cell death. Necroptosis is implicated in combating infections, but also in contributing to numerous other clinical conditions, including cardiovascular diseases and neurodegenerative disorders. Inhibition of necroptosis is therefore of therapeutic interest.

Relationship between Multiple Sclerosis-Associated Risk Allele Variants and Circulating T Cell Phenotypes in Healthy Genotype-Selected Controls.

Single nucleotide polymorphisms (SNPs) in or near the gene, that encodes the interleukin-2 (IL-2) receptor α (CD25), are associated with increased risk of immune-mediated diseases including multiple sclerosis (MS). We investigated how the MS-associated SNPs rs2104286 and rs11256593 are associated with CD25 expression on T cells ex vivo by multiparameter flow cytometry in paired genotype-selected healthy controls. We observed that MS-associated SNPs rs2104286 and rs11256593 are associated with expression of CD25 in CD4 but not CD8 T cells.

Perfluorinated substances, risk factors for multiple sclerosis and cellular immune activation.

Perfluorinated alkylated substances (PFASs) have immunomodulatory effects but the impact on multiple sclerosis (MS) and cellular immune functions is only sparsely described. In the present study, we found lower concentrations of the long chain PFAS perfluorooctane sulfonic acid (PFOS) in MS than in healthy controls (HC). In HC, we did not detect associations between PFOS concentrations and immune phenotypes.

GPR15 T cells are Th17 like, increased in smokers and associated with multiple sclerosis.

Smoking is a risk factor for the development and progression of multiple sclerosis (MS); however, the pathogenic effects of smoking are poorly understood. We studied the smoking-associated chemokine receptor-like molecule GPR15 in relation to relapsing-remitting MS (RRMS). Using microarray analyses and qPCR we found elevated GPR15 in blood cells from smokers, and increased GPR15 expression in RRMS.

Alcohol consumption in adolescence is associated with a lower risk of multiple sclerosis in a Danish cohort.

Background And Objective: Due to the possible existence of a vulnerable period of multiple sclerosis (MS) susceptibility in adolescence and because Danish teenagers have a high alcohol consumption, we investigated the association between alcohol consumption at ages 15-19 and the risk of developing MS.

Methods: A total of 1717 patients with MS and 4685 healthy blood donors filled in a comprehensive environmental and lifestyle questionnaire. Data were analysed by logistic regression models and adjusted for selected confounders.

Prognostic value of cerebrospinal fluid neurofilament light chain and chitinase-3-like-1 in newly diagnosed patients with multiple sclerosis.

Background: Neurofilament light chain (NFL) and chitinase-3-like-1 (CHI3L1) concentrations in cerebrospinal fluid (CSF) may have prognostic value in clinically isolated syndromes (CIS) and relapsing-remitting multiple sclerosis (RRMS).

Objectives: To compare the prognostic value of CSF concentrations of NFL and CHI3L1 in newly diagnosed CIS and RRMS patients.

Methods: NFL and CHI3L1 were measured in CSF in 177 newly diagnosed patients with CIS or RRMS who were followed clinically for a mean of 5.

Smoking affects the interferon beta treatment response in multiple sclerosis.

Objective: To investigate whether smoking in patients with relapsing-remitting multiple sclerosis (RRMS) treated with interferon beta (IFN-β) is associated with the relapse rate and whether there is an interaction between smoking and human leukocyte antigen (HLA)-DRB1*15:01, HLA-A*02:01, and the N-acetyltransferase-1 () variant rs7388368A.

Methods: DNA from 834 IFN-β-treated patients with RRMS from the Danish Multiple Sclerosis Biobank was extracted for genotyping. Information about relapses from 2 years before the start of treatment to either the end of treatment or the last follow-up visit was obtained from the Danish Multiple Sclerosis Treatment Register.

The interaction between smoking and HLA genes in multiple sclerosis: replication and refinement.

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case-control studies from five different countries (Sweden, Denmark, Norway, Serbia, United States).

Genetic burden of MS risk variants distinguish patients from healthy individuals but are not associated with disease activity.

Weighted genetic risk score (wGRS) was analysed for association with disease activity in more than 500 MS patients before and during interferon-beta treatment. The wGRS was higher in MS patients than in healthy controls when analysing eight HLA - and 109 non-HLA MS risk gene variants. No significant associations were observed between number of relapses prior to or during treatment with interferon-beta, both with and without HLA risk alleles included in the wGRS.

Vitamin D supplementation reduces relapse rate in relapsing-remitting multiple sclerosis patients treated with natalizumab.

Background: Vitamin D insufficiency is common among multiple sclerosis patients, and hypovitaminosis D has been associated with multiple sclerosis (MS) risk and disease activity.

Objective: To investigate how recommendations on vitamin D3 supplements affect 25-hydroxyvitamin D (25(OH)D) levels in patients with relapsing-remitting MS (RRMS) and to examine the clinical effects associated with changes in 25(OH)D levels.

Methods: In this prospective cohort study, baseline blood samples were collected from 170 natalizumab-treated RRMS patients during winter 2009-2010 and were repeated the following winter.

Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.

Objective: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS).

Methods: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration.

Association between age at onset of multiple sclerosis and vitamin D level-related factors.

Objective: To compare vitamin D level-associated single-nucleotide polymorphisms (SNPs) in GC and CYP2R1, multiple sclerosis (MS) risk SNPs in CYP27B1, CYP24A1, and HLA-DRB1*1501, and adolescent exposure to environmental risk factors for hypovitaminosis D, with MS age at onset.

Methods: This cross-sectional study included 1161 Danish patients with MS; lifestyle questionnaires and blood samples for genotyping were collected from all participants from 2009 to 2012. Information on age at onset was obtained from the Danish MS Treatment Registry.