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Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.ORCID iD: 0000-0001-9581-3845
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
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2013 (English)In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 12, 1587-1591 p.Article in journal (Refereed) Published
Abstract [en]

Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.

Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.

Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.

Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.

Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.

Place, publisher, year, edition, pages
Sage Publications, 2013. Vol. 19, no 12, 1587-1591 p.
Keyword [en]
Multiple sclerosis, Case control study, Risk factors in epidemiology, Epstein-Barr virus (EBV), Epstein-Barr Nuclear Antigen-1 (EBNA-1), Vitamin D (25[OH]D)
National Category
Neurology
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-63746DOI: 10.1177/1352458513483888ISI: 000325696100008OAI: oai:DiVA.org:umu-63746DiVA: diva2:582959
Available from: 2013-02-11 Created: 2013-01-07 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Environmental risk factors for multiple sclerosis
Open this publication in new window or tab >>Environmental risk factors for multiple sclerosis
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Miljöfaktorers betydelse för multipel skleros
Abstract [en]

Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It usually strikes during young adulthood, and 2.5 million individuals are estimated to have the disease worldwide. The causes of MS are not known, but several factors have been shown to be associated with the risk of the disease, including certain genes, vitamin D, smoking and Epstein- Barr virus infection. Little is known about how/if these factors interact.

Methods Study I: The risk of MS by month of birth was investigated using MS cases from the Swedish MS registry and using general population controls. Studies II–V: We identified MS cases who had donated blood prior to disease onset, and MS cases whose mothers had donated blood during pregnancy, by cross-linking a database of MS cases, and a database of mothers of MS cases, to two local biobank cohorts. One of them consisted of blood samples collected during early pregnancy, and one with samples collected during health controls. Levels of 25(OH)D (25-hydroxyvitamin D), RBP (retinol binding protein, a surrogate marker for vitamin A), CRP (C- reactive protein), cotinine (a nicotine metabolite) and anti Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibodies were measured in cases and matched controls. The risk of MS by categories of these exposures was estimated in bi- and multivariable matched logistic regression models.

Results Subjects born in spring had a higher risk of MS, but no influence of early gestational levels of the measured risk factors on the risk of MS in the offspring was observed. In prospective samples from MS cases and controls, 25(OH)D levels ≥75 nmol/l, intermediate RBP levels, and elevated CRP levels in young were associated with a decreased risk of MS. Elevated cotinine levels (suggestive of smoking) and high antibody reactivity against EBNA-1 were associated with an increased risk of MS. All factors but RBP were more clearly associated with MS in young subjects.

Conclusion All factors analyzed in prospectively collected samples were associated with the risk of MS, and taken together, the data indicate that the key etiopathological events that lead to MS occur before the age of 20–30. Study II provides support for trials exploring the primary preventive potential of oral vitamin D supplementation.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2013. 54 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1545
Keyword
Multiple sclerosis, risk factors in epidemiology, prospective, month of birth, vitamin D, vitamin A, C-reactive protein, hygiene hypothesis, smoking, cotinine, Epstein-Barr virus
National Category
Neurology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-64212 (URN)978-91-7459-545-1 (ISBN)
Public defence
2013-03-01, Hörsal E04, By 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-02-08 Created: 2013-01-21 Last updated: 2013-02-08Bibliographically approved

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Salzer, JonatanNyström, MariaHallmans, GöranStenlund, HansWadell, GöranSundström, Peter
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