scholarly journals Vitamin D status and antibody levels to common viruses in pediatric-onset multiple sclerosis

2011 ◽  
Vol 17 (6) ◽  
pp. 666-671 ◽  
Author(s):  
Ellen M Mowry ◽  
Judith A James ◽  
Lauren B Krupp ◽  
Emmanuelle Waubant
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Disease Status ◽  
Nuclear Antigen ◽  
Vitamin D Status ◽  
Vitamin D Levels ◽  
Remote Infection ◽  
Epstein Barr ◽  
Antibody Levels ◽  
Pediatric Onset

Background: The relative contribution and interaction of risk factors for multiple sclerosis (MS) have not been evaluated. Objectives: To determine whether vitamin D status is associated with antibody levels to common viruses in pediatric-onset MS or clinically isolated syndrome (CIS) patients and controls. Methods: We assessed whether vitamin D status was associated with viral antibody levels to Epstein–Barr virus, cytomegalovirus (CMV), and herpes simplex virus (HSV)-1 or -2 in subjects who demonstrated evidence of remote infection with these viruses and whether these associations differed depending on disease status. Results: In 140 subjects, vitamin D status was weakly associated with antibody levels to CMV but not to the other viruses. However, there were some interactions between vitamin D status and disease state. Among those with vitamin D sufficiency (≥30 ng/ml), MS/CIS patients had higher antibody levels to Epstein–Barr nuclear antigen-1 than controls. Vitamin D sufficiency was associated with higher CMV antibody levels in MS/CIS subjects but lower CMV antibody levels in controls. Higher vitamin D levels appeared to be associated with higher titers to HSV-2 in MS/CIS patients but not controls. Conclusions: Vitamin D status may be differentially associated with antibody levels to common childhood viruses among seropositive subjects.

scholarly journals Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk

2019 ◽  
Vol 116 (34) ◽  
pp. 16955-16960 ◽  
Author(s):  
Katarina Tengvall ◽  
Jesse Huang ◽  
Cecilia Hellström ◽  
Patrick Kammer ◽  
Martin Biström ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Molecular Mimicry ◽  
Nuclear Antigen ◽  
Immune Reactivity ◽  
Barr Virus ◽  
Epstein Barr ◽  
Antibody Levels

Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 × 10−36) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95%CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15:01 carriage, absence of HLA-A*02:01, and high anti-EBNA1 antibody levels (OR = 24.9; 95%CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLA-DRB1*04:01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95%CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.

Vitamin D, HLA-DRB1 and Epstein-Barr virus antibody levels in a prospective cohort of multiple sclerosis patients

2016 ◽  
Vol 23 (6) ◽  
pp. 1064-1070 ◽  
Author(s):  
S. Wergeland ◽  
K.-M. Myhr ◽  
K. I. Løken-Amsrud ◽  
A. G. Beiske ◽  
K. S. Bjerve ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Prospective Cohort ◽  
Epstein Barr Virus ◽  
Virus Antibody ◽  
Barr Virus ◽  
Epstein Barr ◽  
Multiple Sclerosis Patients ◽  
Antibody Levels

Multiple sclerosis-associated retrovirus, Epstein-Barr virus, and vitamin D status in patients with relapsing remitting multiple sclerosis

2017 ◽  
Vol 89 (7) ◽  
pp. 1309-1313 ◽  
Author(s):  
Aliehossadat Mostafa ◽  
Somayeh Jalilvand ◽  
Zabihollah Shoja ◽  
Ahmad Nejati ◽  
Shohreh Shahmahmoodi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Epstein Barr Virus ◽  
Vitamin D Status ◽  
Barr Virus ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Epstein Barr ◽  
Relapsing Remitting Multiple Sclerosis

Season of infectious mononucleosis and risk of multiple sclerosis at different latitudes; the EnvIMS Study

2013 ◽  
Vol 20 (6) ◽  
pp. 669-674 ◽  
Author(s):  
Andreas Lossius ◽  
Trond Riise ◽  
Maura Pugliatti ◽  
Kjetil Bjørnevik ◽  
Ilaria Casetta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Solar Radiation ◽  
Infectious Mononucleosis ◽  
Similar Degree ◽  
Barr Virus ◽  
Vitamin D Levels ◽  
Epstein Barr ◽  
Control Study ◽  
Subsequent Risk

Background: Seasonal fluctuations in solar radiation and vitamin D levels could modulate the immune response against Epstein-Barr virus (EBV) infection and influence the subsequent risk of multiple sclerosis (MS). Methods: Altogether 1660 MS patients and 3050 controls from Norway and Italy participating in the multinational case-control study of Environmental Factors In Multiple Sclerosis (EnvIMS) reported season of past infectious mononucleosis (IM). Results: IM was generally reported more frequently in Norway ( p=0.002), but was associated with MS to a similar degree in Norway (odds ratio (OR) 2.12, 95% confidence interval (CI) 1.64–2.73) and Italy (OR 1.72, 95% CI 1.17–2.52). For all participants, there was a higher reported frequency of IM during spring compared to fall ( p<0.0005). Stratified by season of IM, the ORs for MS were 1.58 in spring (95% CI 1.08–2.31), 2.26 in summer (95% CI 1.46–3.51), 2.86 in fall (95% CI 1.69–4.85) and 2.30 in winter (95% CI 1.45–3.66). Conclusions: IM is associated with MS independently of season, and the association is not stronger for IM during spring, when vitamin D levels reach nadir. The distribution of IM may point towards a correlation with solar radiation or other factors with a similar latitudinal and seasonal variation.

Antibodies to Epstein-Barr virus and MRI disease activity in multiple sclerosis

2014 ◽  
Vol 20 (14) ◽  
pp. 1833-1840 ◽  
Author(s):  
Silje Kvistad ◽  
Kjell-Morten Myhr ◽  
Trygve Holmøy ◽  
Søren Bakke ◽  
Antonie G Beiske ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Activity ◽  
Treatment Response ◽  
Epstein Barr Virus ◽  
Nuclear Antigen ◽  
Inverse Association ◽  
Barr Virus ◽  
T2 Lesions ◽  
Epstein Barr ◽  
Antibody Levels

Background: Previous reports indicate an association between Epstein-Barr virus (EBV) antibody levels and multiple sclerosis (MS) disease activity, but the results have been conflicting. Objectives: The objective of this paper is to study if EBV antibody levels reflect MRI disease activity in MS and examine the potential for EBV antibody levels as biomarkers for treatment response. Methods: A total of 87 MS patients were followed for two years prior to and during interferon beta (IFNB) treatment, with MRI examinations and serum measurement of IgM and IgG antibodies to viral capsid antigen (VCA), EBV nuclear antigen 1 (EBNA-1) and early antigen (EA). Associations between EBV antibody levels and MRI activity were assessed by a logistic regression model. Results: Higher anti-EBNA-1 IgG levels were associated with increased MRI activity, OR = 2.95 (95% CI 1.07–8.10; p = 0.036) for combined unique activity (CUA; the sum of T1Gd+ lesions and new or enlarging T2 lesions). Although most patients were anti-VCA IgM negative, there was an inverse association, OR = 0.32 (95% CI 0.12–0.84; p = 0.021) with CUA during IFNB treatment. Conclusions: This study supports an association between anti-EBNA-1 IgG levels and MS disease activity. We also found an inverse association with anti-VCA IgM levels during IFNB treatment not previously described, indicating anti-VCA IgM as a possible biomarker for IFNB treatment response.

scholarly journals Low sun exposure increases multiple sclerosis risk both directly and indirectly

2019 ◽  
Vol 267 (4) ◽  
pp. 1045-1052 ◽  
Author(s):  
Anna Karin Hedström ◽  
Tomas Olsson ◽  
Ingrid Kockum ◽  
Jan Hillert ◽  
Lars Alfredsson
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Sun Exposure ◽  
Population Based ◽  
Total Effect ◽  
Mediation Effect ◽  
Vitamin D Status ◽  
Case Control Studies ◽  
Vitamin D Levels

Abstract Objective We aimed to study (1) to what extent the influence of low sun exposure on multiple sclerosis (MS) risk is mediated by low vitamin D levels; (2) whether low sun exposure or vitamin D deficiency act synergistically with HLA-DRB1*15:01 and absence of HLA-A*02:01. Methods We used two population-based case–control studies (7069 cases, 6632 matched controls). Subjects with different HLA alleles, sun exposure habits and vitamin D status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Mediation analysis was used to identify the potential mediation effect of vitamin D on the relationship between low sun exposure and MS risk. Results Low sun exposure increased MS risk directly as well as indirectly, by affecting vitamin D status. The direct effect, expressed as OR, was 1.26 (95% CI 1.04–1.45) and the indirect effect, mediated by vitamin D deficiency, was 1.10 (95% CI 1.02–1.23). Of the total effect, nearly 30% was mediated by vitamin D deficiency. There was a significant interaction between low sun exposure and vitamin D deficiency (attributable proportion due to interaction 0.3, 95% CI 0.04–0.5) accounting for about 12% of the total effect. Further, both factors interacted with HLA-DRB1*15:01 to increase MS risk. Interpretation Our findings indicate that low sun exposure acts both directly on MS risk as well as indirectly, by leading to low vitamin D levels. The protective effect of sun exposure thus seems to involve both vitamin D and non-vitamin D pathways, which is of relevance for prevention, in particular for those with a genetic susceptibility to MS.

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