scholarly journals Some aspects of the pathogenesis of multiple sclerosis

2021 ◽  
Vol XXX (3-4) ◽  
pp. 60-64
Author(s):  
Т. V. Matveeva ◽  
М. I. Arleevskaya ◽  
Т. V. Demin
Keyword(s):  
Multiple Sclerosis ◽  
Impulse Conduction ◽  
Genetically Determined

The key mechanism of the pathogenesis of multiple sclerosis (MS) is demyelination and the associated impairment of axonal impulse conduction. This disease is genetically determined to a certain extent.

scholarly journals BMI and low vitamin D are causal factors for multiple sclerosis

2020 ◽  
Vol 7 (2) ◽  
pp. e662 ◽  
Author(s):  
Benjamin M. Jacobs ◽  
Alastair J. Noyce ◽  
Gavin Giovannoni ◽  
Ruth Dobson
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Meta Analysis ◽  
Serum Vitamin ◽  
Sensitivity Analyses ◽  
Serum Vitamin D ◽  
Adult Body Mass ◽  
Inverse Variance ◽  
Unit Increase ◽  
Genetically Determined

ObjectiveTo update the causal estimates for the effects of adult body mass index (BMI), childhood BMI, and vitamin D status on multiple sclerosis (MS) risk.MethodsWe used 2-sample Mendelian randomization to determine causal estimates. Summary statistics for SNP associations with traits of interest were obtained from the relevant consortia. Primary analyses consisted of random-effects inverse-variance-weighted meta-analysis, followed by secondary sensitivity analyses.ResultsGenetically determined increased childhood BMI (ORMS 1.24, 95% CI 1.05–1.45, p = 0.011) and adult BMI (ORMS 1.14, 95% CI 1.01–1.30, p = 0.042) were associated with increased MS risk. The effect of genetically determined adult BMI on MS risk lessened after exclusion of 16 variants associated with childhood BMI (ORMS 1.11, 95% CI 0.97–1.28, p = 0.121). Correcting for effects of serum vitamin D in a multivariate analysis did not alter the direction or significance of these estimates. Each genetically determined unit increase in the natural-log-transformed vitamin D level was associated with a 43% decrease in the odds of MS (OR 0.57, 95% CI 0.41–0.81, p = 0.001).ConclusionsWe provide novel evidence that BMI before the age of 10 is an independent causal risk factor for MS and strengthen evidence for the causal role of vitamin D in the pathogenesis of MS.

scholarly journals Circulating Interleukins and Risk of Multiple Sclerosis: A Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui Lu ◽  
Peng-Fei Wu ◽  
Wan Zhang ◽  
Xiaoyao Liao
Keyword(s):  
Multiple Sclerosis ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Standard Deviation Increase ◽  
Α Subunit ◽  
Genome Wide ◽  
Level Data ◽  
Genetically Determined ◽  
Circulating Levels

BackgroundPrevious research have implicated critical roles of systemic inflammation in the development of Multiple Sclerosis (MS). But the causal relationship between interleukins (ILs) and MS has not been fully elucidated.ObjectiveIn this study, we applied Mendelian randomization (MR) approaches to address the causal associations between genetically determined circulating levels of ILs and the risk of MS.MethodsGenetic instruments for circulating IL-1 receptor antagonist (IL-1Ra), IL-2 receptor α subunit (IL-2Rα), IL-6, IL-16, IL-17, and IL-18 were obtained from recently published genome-wide association studies (GWAS). Summary-level data for MS were obtained from the International Multiple Sclerosis Genetics Consortium. MR analyses were performed using the R software (version 3.6.1, The R Foundation) and the TwoSampleMR package.ResultsGenetic predisposition to higher circulating levels of IL-2Rα were significantly associated with MS risk. The odds ratio (OR) was 1.22 (95% confidence interval [CI], 1.12–1.32; p < 0.001) per one standard deviation increase in circulating IL-2Rα levels. There was a suggestive association of circulating IL-1Ra with MS risk (OR, 0.94; 95% CI, 0.88–0.99; p = 0.027). The other ILs were not associated with the outcome.ConclusionOur results indicated that circulating IL-2Rα was causally associated with risk of MS.

Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid are less likely to develop neutralizing antibodies against interferon beta

2010 ◽  
Vol 16 (7) ◽  
pp. 796-800 ◽  
Author(s):  
M. Lundkvist ◽  
E. Greiner ◽  
J. Hillert ◽  
A. Fogdell-Hahn
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Oligoclonal Bands ◽  
Distinct Subgroup ◽  
Oligoclonal Igg ◽  
Multiple Sclerosis Patients ◽  
Genetically Determined ◽  
Oligoclonal Igg Bands

Multiple sclerosis patients without cerebrospinal fluid oligoclonal IgG bands have been proposed to constitute an immunogenetically distinct subgroup of multiple sclerosis that may also differ in terms of prognosis. A proportion of patients with multiple sclerosis receiving IFNβ develop neutralizing antibodies, which interfere with treatment efficacy. Evidence suggests that the likelihood of developing neutralizing antibodies is partly genetically determined. Here, we hypothesized that absence of oligoclonal IgG bands reflects a property of B-cell responses in oligoclonal IgG band-negative patients characterized by a lessened propensity to develop neutralizing antibodies. We aimed to compare the development of neutralizing antibodies against IFNβ between oligoclonal IgG band-negative and oligoclonal IgG band-positive multiple sclerosis patients. Treatment, oligoclonal IgG band and neutralizing antibody information was obtained for 2219 patients from the Swedish multiple sclerosis registry and the Swedish neutralizing antibody registry. Additional data on genotype was available for 532 patients. A correlation was found between oligoclonal IgG band negativity and neutralizing antibody negativity ( p = 0.02). This difference was confined to neutralizing antibodies against IFNβ-1a, since oligoclonal IgG band-negative patients were, to a lesser extent, neutralizing antibody positive compared with oligoclonal IgG band-positive patients if treated with IFNβ-1a (12% vs. 23%; p = 0.005). No difference was observed for IFNβ-1b-treated patients (44% vs. 46%). We propose that oligoclonal IgG band-negative patients differ immunologically from oligoclonal IgG band-positive patients, potentially influenced by distinct HLA-DRB1 alleles.

Ultrastructural alterations in the fetal mouse myocardium in response to genetic and environmental factors

1987 ◽  
Vol 45 ◽  
pp. 724-725
Author(s):  
K.C. Feng-Chen ◽  
F.B. Essien ◽  
K.J. Prestwidge ◽  
J.T. Cheng ◽  
C.L. Shen
Keyword(s):  
Fetal Heart ◽  
Perinatal Period ◽  
Primary Energy ◽  
Cardiac Contraction ◽  
Ultrastructural Changes ◽  
Fetal Mouse ◽  
The Subject ◽  
Physiological Adjustments ◽  
Genetic And Environmental Factors ◽  
Genetically Determined

The physiology of the fetal heart differs significantly from that of the mature post-natal organ: e.g., the metabolic supply for adult cardiac contraction relies mainly on fatty acids; whereas, the fetal heart uses carbohydrates as its primary energy source. Limited morphological descriptions of the developing myocardium have appeared. However, additional studies are required to elucidate the ultrastructural changes occuring in the perinatal period when enormous physiological adjustments are made. Although adult animals are most often used in toxocological and pathological analyses, it is also important to investigate fetal cardiac responsiveness to various agents. The vulnerability of the ultrastructure of the fetal mouse myocardium to genetic and environmental assault is the subject of this report. The genetically determined effect on the heart was observed in mouse embryos homozygous for the cab (cardiac abnormality) mutation discovered by Essien.

Microglia-derived macrophages in early multiple sclerosis plaques

1996 ◽  
Vol 22 (3) ◽  
pp. 207-215 ◽  
Author(s):  
H. Li ◽  
M. L. Cuzner ◽  
J. Newcombe
Keyword(s):  
Multiple Sclerosis
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