Risk Of Developing Multiple Sclerosis Research Articles

The level of anti-viral antigen-specific antibodies to EBNA-1 in the serum of ms patients does not depend on the severity of the disease

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease leading to inevitable disability and primarily affecting the young and middle-aged population. Recent studies have shown a direct correlation between the risk of MS development and Epstein-Barr virus (EBV) infection. Analysis of the titer of EBV-specific antibodies among patients with MS and healthy donors among Russian population confirmed that MS is characterized by an increased level of serum IgG binding EBNA-1 (EBV nuclear antigen 1). The number of patients with elevated levels of EBNA-1-specific antibodies does not differ statistically significantly between two groups with diametrically opposite courses of MS: benign MS or highly active MS. It can be assumed that the primary link between EBV and the development of MS is restricted to the initiation of the disease and does not impact its severity.

The Level of Anti-Viral Antigen-Specific Antibodies to EBNA-1 in the Serum of MS Patients Does not Depend on the Severity of the Disease

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease leading to inevitable disability and primarily affecting the young and middle-aged population. Recent studies have shown a direct correlation between the risk of MS development and Epstein–Barr virus (EBV) infection. Analysis of the titer of EBV-specific antibodies among patients with MS and healthy donors among Russian population confirmed that MS is characterized by an increased level of serum IgG binding EBNA-1 (EBV nuclear antigen 1). The number of patients with elevated levels of EBNA-1-specific antibodies does not differ statistically significantly between two groups with diametrically opposite courses of MS: benign MS or highly active MS. It can be assumed that the primary link between EBV and the development of MS is restricted to the initiation of the disease and does not impact its severity.

Adverse Childhood Experiences and the Risk of Multiple Sclerosis Development: A Review of Potential Mechanisms.

Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, contribute to long-term systemic toxic stress and inflammation that may last well into adulthood. Such early-life stressors have been associated with increased susceptibility to multiple sclerosis (MS) in observational studies and with the development of experimental autoimmune encephalomyelitis in animal models. In this review, we summarize the evidence for an ACE-mediated increase in MS risk, as well as the potential mechanisms for this association. ACEs dysregulate neurodevelopment, stress responses, and immune reactivity; they also alter the interplay between the immune system and neural networks. All of this may be relevant for MS risk. We further discuss how ACEs induce epigenetic changes and how the toxic stress caused by ACEs may reactivate the Epstein-Barr Virus (EBV), a key risk factor for MS. We conclude by suggesting new initiatives to obtain further insights into this topic.

Systemic inflammation and risk of multiple sclerosis - A presymptomatic case-control study.

C-reactive protein (CRP) is a marker of systemic inflammation. Increased levels of CRP in young persons have been suggested to decrease the risk of multiple sclerosis (MS). To assess CRP as a risk factor for MS. Levels of CRP were measured with a high-sensitive immunoassay in biobank samples from 837 individuals who later developed MS and 984 matched controls. The risk of developing MS was analysed by conditional logistic regression on z-scored CRP values. Levels of CRP were not associated with MS risk. We found no association between CRP levels and risk of MS development.

Variation of genes encoding nitric oxide synthases and antioxidant enzymes as potential risks of multiple sclerosis development: a preliminary study

Multiple sclerosis (MS) is a neurodegenerative disease characterized by a variable clinical course and diverse pathophysiology, including nitrative and oxidative stresses as well as inflammation. We aimed to detect the potential association between five selected single-nucleotide polymorphisms (SNPs) in genes encoding nitric oxide synthetases as well as antioxidant enzymes and the development of MS in a Polish population. Genomic DNA was isolated from peripheral blood collected from 142 MS patients and 140 controls. Using Taq-Man® probes, we genotyped the following SNPs: rs1879417 in NOS1, and rs2297518 in NOS2 as well as rs4880 in SOD2, rs7943316 in CAT, rs713041 in GPX4. In the case of rs2297518, the C/C genotype and C allele SNP were associated with an enhanced occurrence of MS, while the C/T, T/T genotypes, and T allele of the same polymorphism reduced this risk. Moreover, the C/C homozygote and C allele of the rs4880 SNP reduced MS risk, while the T allele increased the risk. In addition, the A/T heterozygote of rs7943316 polymorphism was associated with an increased risk of MS occurrence. We also detected that the C/C genotype and C allele of rs713041 decreased the risk of MS, whereas the T/T genotype and T allele increased this risk. In conclusion, the results of our study suggest some links between polymorphic variability in the nitrative/oxidative stress-related genes and the risk of MS development in the Polish population.

Air pollution and multiple sclerosis: a comprehensive review

Multiple sclerosis (MS) is an inflammatory, autoimmune demyelinating disorder of the central nervous system (CNS), leading to progressive functional impairments, and many intrinsic and acquired factors are believed to be associated with its development and relapse. In terms of environmental factors, air pollution has gained much attention during recent decades, as chronic exposure to ambient air pollution seems to increase the level of some pro-inflammatory markers in the human brain, which can lead to neuroinflammation, neurodegeneration, and blood-brain barrier (BBB) breakdown. These events may also be associated with the risk of MS development and relapse. In this review, we aimed to summarize recent findings around the impact of air pollutants, including particulate matter (PM10, PM2.5, and ultra-fine particles), gaseous pollutants (carbon monoxide [CO], nitrogen oxides [NOx], sulfur dioxide [SO2], and ozone [O3]), and heavy metals, on MS development and relapse.

Vitamin D and Multiple Sclerosis; Is There a Real Association?

Multiple sclerosis is a demyelinating autoimmune disease that commonly affects young people. Several risk factors are associated with multiple sclerosis, including low vitamin D levels. Vitamin D is essential in various regulatory processes, particularly in the immune system. Fifty years ago, vitamin D was suggested to have a role in the risk of multiple sclerosis development and relapses, which was proposed after reporting seasonal and geographic variation of multiple sclerosis incidence around

A link between promoter polymorphisms of the transforming growth factor β1 (TGFB1) and TGF-β1 receptor II (TGFBR2) genes and relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is achronic progressive autoimmune disease characterised by nerve demyelination, mediated by myelin-specific Th1 autoreactive cells. Transforming growth factor1 (TGF-1) is aregulatory cytokine involved in MS aetiology by maintaining CD4+ cell differentiation and preventing autoimmune responses. Because of the important role of the TGF-1 signalling pathway in MS aetiopathogenesis, we aimed to investigate the association of two DNA polymorphisms: TGFB1C[-509]T and TGFBR2G[-875]Aand their combined genotypes with the risk of MS development in acohort of Bulgarian patients. The effect of the two promoter polymorphisms on the disease onset was also assessed. In the study, acohort of 183 patients with relapsing-remitting multiple sclerosis (RRMS) and 307 sex- and age-matched healthy subjects were recruited. Genotyping of the TGFB1C[-509]T (rs1800469) and TGFBR2G[-875]A(rs3087465) polymorphisms was performed by PCR-RFLP and PIRA-PCR approaches. Frequencies of the TGFB1T[-509]T genotype and TGFB1[-509]*T-allele were lower in RRMS men than in control healthy men (15.7% vs. 26.9%, 37.3% vs. 50.7%, respectively). Among males, the TGFB1T[-509]T genotype was related to asignificantly reduced risk of RRMS (OR = 0.360, 95% CI: 0.126-1.028, p = 0.05) in comparison to the TGFB1C[-509]C genotype. Also, TGFB1[-509]*T-allele was more common in men with RRMS than in healthy men relative to the TGFB1[-509]*C-allele and was associated with astatistically significant protective effect (OR = 0.576, 95% CI: 0.341-0.974, p = 0.039). The combination of TGFB1T[-509]T/TGFB1T[-509]C and TGFBR2G[-875]Agenotypes among men was associated with asignificant protective effect compared to the wild-type homozygous TGFB1C[-509]C and TGFBR2G[-875]G genotypes (OR = 0.268, 95% CI: 0.088-0.818, p = 0.018). No significant association between rs1800469 and rs3087465 was observed among females with and without (controls) RRMS. In summary, we suggest that in males, ahigher TGF-1 level determined by TGFB1T[-509]T genotype in combination with the TGFBR2G[-875]Agenotype might be aprotective factor against RRMS development.

Оценка факторов риска развития рассеянного склероза в Республике Ингушетия

Currently the ubiquitous increase of multiple sclerosis (MS) prevalence is observed. The increase in number of patients with MS is marked also in the areas where MS prevalence was low previously, so the assessment of multiple sclerosis risk factors in populations with low multiple sclerosis risk is of a great value. There were no investigations of demyelinating disease epidemiology performed in the Republic of Ingushetia (RI) before. The purpose. To perform the clinical and epidemiological study of MS in RI; to study the factors, affecting the risk of MS development in RI population. Material and methods. We examined 73 patients (46 women and 27 men) with reliable MS (according to McDonald criteria, 2010, 2017). The investigation of risk factors of MS development was carried out by the method of analytical epidemiology «case-control». All respondents were inhabitants of RI, the pairs were comparable in age, gender and nationality. We studied serum concentration of vitamin D3 metabolite — 25(ОН)D3 by ELISA method. Results. Prevalence of NS in RI was 14.4 cases for 100 thousand of the population as of 1.01.2020. Among MS patients we revealed a higher frequency of contact with petrol and oil products (12 of 73 respondents vs 2 of 61 in groups of MS patients and control group respectively, р < 0,05), and paints (15 of 73 respondents vs 2 of 61 in groups of MS patients and control group respectively, р < 0,05), aged over 15 years old. Reliably more often than persons of control group MS patients have a case of surgical interventions, severe caries at the age over 15 years old (р < 0,05), head injury at any age (р < 0,05), tonsillitis, measles, rubella, parotitis occurred at the age before 7 years old (р < 0,05) and herpetic infection at any age (р < 0,05). According to the comparison of vitamin D3 metabolite — 25(ОН)D3 serum concentration parameters in MS patients of both sexes of RI population and control group we revealed a tendency to decrease of serum vitamin D level in MS patients; the differences in this feature in men with MS (15,15 (0,61) ng/ml) and men of control group (22,04 (8,0) ng/ml) were statistically reliable. Conclusion. The Republic of Ingushetia belongs to the areas of low-mild multiple sclerosis development risk, which is probably due to both demographic and geographical-climatic features. The external factors of MS development risk revealed in this research confirm the multifactor nature of the disease. Further investigations of the probable modifiability of these factors are of great importance.

Variants of Mitochondrial Genome and Risk of Multiple Sclerosis Development in Russians

For the first time in the history of ethnic Russians, an association analysis the development of multiple sclerosis (MS) was performed for the mitochondrial haplogroups H, J, K, and U, as well as for the individual mitochondrial DNA (mtDNA) polymorphisms discriminating these haplogroups (m.1719G > A, m. 7028C > T, m.9055G > A, m.10398A > G, m.12308A > G). A total of 283 unrelated patients with the relapsing-remitting form of MS and 290 healthy controls were enrolled in the study. Association of haplogroup J with MS was observed (P = 0.0055, OR = 2.00 [95% CI 1.21-3.41]). After gender stratification, the association remained significant in women (P = 0.0083, OR = 2.20 [95% CI 1.19-4.03]). A multilocus analysis of the association between combinations of mtDNA haplogroups with variants of 38 nuclear immune-related genes and MS risk was carried out. MS-associated biallelic combinations of haplogroup J with the alleles CCL5 rs2107538*A, PVT1 rs2114358*G, TNFSF14 rs1077667*C, and IL4 rs2243250*C, which were not associated with MS individually, were identified. For the combination of haplogroup J and the CCL5*A allele (P = 0.00043, OR = 5.47 [95% CI 1.85-16.15]), a epistatic (synergistic) interaction between the components was established using two statistical criteria: the PFLINT value in the Fisher-like interaction numeric test and the synergy factor, SF (PFLINT = 0.025, SF = 4.32 [95% CI 1.20-15.60]). The combination of haplogroup J and the PVT1*G allele is characterized by PFLINT = 0.084; SF = 3.05 [95% CI 1.00-9.31] and can also be epistatic. Thus, interaction between nuclear and mitochondrial genome components in the risk of developing MS was demonstrated for the first time.

Analysis of ICAM1 gene polymorphism in Slovak multiple sclerosis patients.

Infiltration of immune cells into CNS is one of the essential events in multiple sclerosis (MS) development. Adhesion molecules like the intercellular adhesion molecule 1 (ICAM-1) play critical role in this process. Therefore, the ICAM1 gene containing two important single-nucleotide polymorphisms (SNPs) belongs to candidate loci with possible involvement in MS susceptibility and/or severity. The objective of our case-control study was to analyze the association of two functional ICAM1 polymorphisms rs1799969 (or G241R) and rs5498 (or K469E) with susceptibility to MS and evaluate their influence on the age at disease onset, severity, neurological disability and progression rate. Two hundred forty-eight MS subjects (mean 39.2years) and 208 age-matched controls (mean 35.6years) were involved in the study. Genotyping of ICAM1 rs1799969 and rs5498 SNPs was performed by PCR-RFLP. Presence of the rs3135388 polymorphism tagging the major MS risk allele HLA-DRB1*15:01 allele was determined as well. Our analysis revealed no statistically significant association of ICAM1 polymorphisms with risk of MS development in the Slovak population. Stratification of study cohorts by gender, age at onset and presence of the HLA-DRB1*15:01 risk allele showed only moderate changes. Correlation of clinical findings as age at onset, Kurtzke Expanded Disability Status Scale, Multiple Sclerosis Severity Score and progression index with ICAM1 genotypes in MS patients revealed no significant association; however, patients with earlier onset of MS showed slightly higher frequencies of the homozygous G allele at rs5498 in comparison to other genotypes (P=0.04), suggesting that GG carriers tend to induce MS at an earlier age.

CYTOKINES AND HERPESVIRUSES IN CHILDREN WITH MULTIPLE SCLEROSIS

It was determined earlier (G.P. Ivanova, 2012) that a chronic course of leukoencephalitis in teenagers caused by inadequate response of cytokine system to the combination of two herpesviruses (HV) — EBV and HHV-6, leads to the development of multiple sclerosis (MS) in 44% of cases. The research objective was to characterize the cytokine response in children with MS with simultaneous screening of the presence of active HV infections. 39 children with the diagnosis “MS” were under observation, 34 of them had relapsing-remitting (RR) MS, and 5 children had a progressing course of MS (PMS). Concentration of cytokines IL-1β, IL-6, IL-8, IL-10, IFNα, IFNγ, and IL-4 was identified in blood serum and cerebrospinal liquid (CSF) by enzyme-linked immunosorbent assay, HV DNA was revealed by PCR. Cytokine status in children with MS had some differences depending on the phase of the disease, clinical severity of the relapse and the course of MS. The relapse phase of RRMS was associated with the accumulation of IL-8, IL-10, and IL-6 in the blood, and index IFNγ/IL-4 modulations in accordance with the clinical severity of the relapse. A severe aggravation of the disease in children with PMS was accompanied by the increase of IL-8 system response. HV DNA was revealed in 27 patients from 39 ones (69%) in blood and in 17 patients (44%) in CSF with the predominance of EBV (93%), frequently in combination with HHV-6. During an acute period the frequency of HV DNA identification increased 2–3 times to compare with the remission period. Unlike children with RRMS, a mixed-infection of 3–4 herpes viruses was revealed in all 5 patients with PMS. According to the results summary it is possible to make a conclusion that HV-infection has an important role in MS pathogenesis in teenagers, taking part in the aggravation and progression of the disease by its effect on the cytokine system response. EBV-infection dominates among HV, however the risk of MS development increases to a great extent in the case of EBV association with another lymphotropic virus — HHV-6.

Managing the complexity of multiple sclerosis

The application of imaging biomarkers has provided new insights into the mechanisms of damage in multiple sclerosis (MS) and the risk of MS development and progression. The goal of eliminating all disease activity requires a timely escalation of treatment. This increasing complexity is compounded by the need to treat comorbidities.

Human Immunodeficiency Virus and Multiple Sclerosis Risk: Probing for a Connection

Multiple Sclerosis (MS) is a chronic autoimmune inflammatory disease of the nervous system, with intense genetic and environmental background. Its etiologyis poorly understood and likely multifactorialbutits epidemiology has been intensively studied. This complex disease displays heterogeneity in terms of geographic and genetic influences on incidence,insinuating an effect of local unknown environmental factors on its development.Among numerous potential factors putatively involved in the etiopathogenesis of MS, retroviruses appear to influence MS. The intent of this review is to highlight the association between human immunodeficiency virus (HIV) and the risk of developing MS while at the same time providing an overview of the insights gleaned from different studies. HIV infection is associated with a reduced risk of MS development, and perhaps, appears to be another wedge of the MS conundrum. The probable mechanisms for this relationship may be suppression of the immune system and/or antiretroviral drug therapy. While highlighting the relevance of antiretroviral medications as potential future alternatives for the effective treatment of MS, this review provides an impetus for further studies. We conclude that studies in this milieu hitherto are insufficient, and there is need for an upsurge in molecular epidemiological and clinical studies, with focus on the mechanism behind the impact of HIV/antiretroviral drugs on MS. Such inquiry could precisely establish the causes for associations between HIV and MS, perhaps impacting treatment options for both.

İZOLE BİLATERAL OPTİK NÖRİT İLE PREZENTE OLAN PEDİYATRİK AKUT DİSSEMİNE ENSEFALOMYELİT OLGUSU

Acute disseminated encephalomyelitis (ADEM) is an inflammatory disease which ischaracterized by demyelination of the central nervous system. Optic neuritis is the most commonophthalmic manifestation of the disease. Various neurological symptoms can be seen accordingto the extent of the disease. Because of the increased risk of multiple sclerosis development;diagnosis, treatment and follow-up of ADEM is essential. Our aim was to present a case ofpediatric ADEM, which presented with optic neuritis alone in the light of current literature

The four seasons of multiple sclerosis

Multiple sclerosis (MS) affects 1–2 per 1,000 people in North America and has a complex etiology that is not fully understood (www.nmss.org), though the immune system plays a major role. Rapidly accumulating studies have identified several genes related to MS susceptibility; most of these encode proteins with immune functions. Furthermore, environmental factors affect both risk for MS development and MS activity. Perhaps the most well-known environmental factor affecting MS is geographic latitude.1 However, the latitudinal gradient appears to be decreasing with time, a finding that may be due to changing environmental factors.2 Interestingly, several regions of the world report an increasing female to male ratio, which has also been attributed to changing environmental factors that affect women differently than men. Environmental factors purported to play a role in risk of MS development or progression include viruses such as Epstein-Barr virus (EBV), vitamin D levels, and smoking, as well as diet, obesity, pregnancy, hormones, and stress. Of these, vitamin D and infections have the clearest seasonality. Vitamin D levels fluctuate along with ultraviolet light exposure, which changes with season.3 Regarding infections, Sibley and colleagues4 reported that the frequency of MS relapses is 3 times higher in periods related to viral infections. Such observations are in accord with the finding that interferon-γ, …

Polymorphism of the prion protein gene PRNP and risk of multiple sclerosis development in ethnic Russians from Bashkortostan

M129V polymorphism of prion protein gene PRNP has been studied in patients with multiple sclerosis (MS) and healthy ethnic Russians from Bashkortostan using allele-specific PCR. The genotype frequency distribution of the examined polymorphism in Russians from Bashkortostan was similar to that in European populations. MM, MV, and VV genotype frequencies in control group and in the MS patients were 50.24%, 42.58%, 7.18% and 43.33%, 45.83%, 10.84%, respectively. It was shown that in the group of MS patients with onset of the disease at the age of 21 and older, the frequency of the VV genotype was higher than in the control group (14.3% versus 6.18%, respectively, P = 0.041). We suggest that the VV genotype is associated with higher risk factor of MS development in the patients aged 21 years and older.

The relationship between HLA-DRB1 alleles and optic neuritis in Irish patients and the risk of developing multiple sclerosis

Aims:To investigate the role of the major histocompatibility complex in Irish patients with optic neuritis (ON) and determine whether HLA-DRB1 genotypes are a risk factor for the development of multiple...

Type 1 Diabetes and Multiple Sclerosis

Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported. To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. Two population-based disease registers, the Danish Hospital Discharge Register and the Danish Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil Registration System. Patients with T1D and first-degree relatives of patients with MS were followed up for occurrence of MS and T1D, respectively, and the relative risks were expressed as standardized incidence ratios, that is, ratios of observed to expected numbers of outcomes based on national age, sex, and period-specific MS and T1D incidence rates. Patients with T1D were at more than 3-fold increased risk for development of MS (relative risk, 3.26; 95% confidence interval, 1.80-5.88; n = 11). First-degree relatives of patients with MS were at 63% increased risk (relative risk, 1.63; 95% confidence interval, 1.26-2.12; n = 56) for development of T1D. However, adjusting for familial relationship to patients with T1D reduced the excess risk to 44% (relative risk, 1.44; 95% confidence interval, 1.11-1.88; n = 56). The present nationwide cohort study demonstrates an intraindividual and, to a lesser degree, an intrafamilial co-occurrence of MS and T1D.

Vitamin D and Autoimmune Disease—Implications for Practice from the Multiple Sclerosis Literature

Recent studies and commentaries link vitamin D with several autoimmune diseases, including multiple sclerosis (MS). Adequate vitamin D intake reduces inflammatory cytokines through control of gene expression, thus inadequate vitamin D intake is suggested as a mechanism that could contribute to inflammation and, consequently, development of MS. Poor vitamin D status has been associated with increased risk for development of MS, and patients with MS may suffer consequences of vitamin D deficiency, such as bone loss. Animal studies and very limited human data suggest possible benefit from vitamin D supplementation in patients with MS. Based on the current state of research, a key principle for practicing dietetics professionals is to include vitamin D status in nutritional assessment. For those at risk for poor vitamin D status, intake can be enhanced by food-based advice and, when indicated, vitamin D supplementation.