Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation.

Leibowitz, Uri; Antonovsky, Aaron; Medalie, J M; Smith, Hilton A.; Halpern, L.; Alter, Milton

doi:10.1136/jnnp.29.1.60

Cited by 146 publications

(84 citation statements)

References 24 publications

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“…MS has been studied in connection with many common viruses, and according to the hygiene hypothesis several infections during early childhood are protective, 3 but if infection occurs later in life there is an increased risk for MS. 4,5 Of note, infectious mononucleosis (IM) and MS share a similar pattern in geographical distribution, socioeconomic status and ethnicity. 6 Compared with controls, MS patients often show elevated levels of antibody reactivity against EBVrelated antigens such as viral capsid antigen, Epstein Barr nuclear antigen 1 (EBNA1) 7,8 and several EBNA1 domains, in particular the 385-420 amino-acid domain.…”

Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus and multiple sclerosis: interaction with HLA

et al. 2011

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Epstein-Barr virus (EBV) infection, history of infectious mononucleosis (IM)and HLA-A and DRB1 have all been proposed as risk factors for multiple sclerosis (MS). Our aim was to analyse possible interactions between antibodies against Epstein-Barr virus nuclear antigen 1 (EBNA1) or EBNA1 fragments, presence of DRB1*15 and absence of A*02. The study population includes newly diagnosed cases and matched controls. Interaction on the additive scale was calculated using attributable proportion due to interaction (AP), which is the proportion of the incidence among individuals exposed to two interacting factors that is attributable to the interaction per se. IM showed association with MS, odds ratio (OR) ¼ 1.89 (1.45-2.48% confidence interval (CI)), as did raised EBNA1 IgG OR ¼ 1.74 (1.38-2.18 95%CI). All EBNA1 fragment IgGs were associated with MS risk. However, EBNA1 fragment 385-420 IgG levels were more strongly associated to MS than total EBNA1 IgG, OR ¼ 3.60 (2.75-4.72 95%CI), and also interacted with both DRB1*15 and absence of A*02, AP 0.60 (0.45-0.76 95%CI) and AP 0.39 (0.18-0.61 95%CI), respectively. The observed interaction between HLA class I and II genotype and reactivity to EBV-related epitopes suggest that the mechanism through which HLA genes influence the risk of MS may, at least in part, involve the immune control of EBV infection.

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Section: Introductionmentioning

confidence: 99%

Epstein-Barr virus and multiple sclerosis: interaction with HLA

et al. 2011

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“…Factors that coincide with these epidemiological findings include the improved health of increasingly prosperous populations and the relative reduction of infections compared with less-developed countries (1). These observations have led to the emergence of the "hygiene hypothesis," which posits that exposure to infectious or environmental agents diminishes the subsequent risk of atopic and autoimmune disease (2,3). The mechanisms underlying this well-recognized phenomenon remain unknown.…”

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confidence: 99%

Early Life Exposure to Lipopolysaccharide Suppresses Experimental Autoimmune Encephalomyelitis by Promoting Tolerogenic Dendritic Cells and Regulatory T Cells

Ellestad

Tsutsui

Noorbakhsh

et al. 2009

The Journal of Immunology

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The rising incidence of autoimmune diseases such as multiple sclerosis (MS) in developed countries might be due to a more hygienic environment, particularly during early life. To investigate this concept, we developed a model of neonatal exposure to a common pathogen-associated molecular pattern, LPS, and determined its impact on experimental autoimmune encephalomyelitis (EAE). Mice exposed to LPS at 2 wk of age showed a delayed onset and diminished severity of myelin oligodendrocyte glycoprotein (MOG)-induced EAE, induced at 12 wk, compared with vehicle-exposed animals. Spinal cord transcript levels of CD3ε and F4/80 were lower in LPS- compared with PBS-exposed EAE animals with increased IL-10 levels in the LPS-exposed group. Splenic CD11c+ cells from LPS-exposed animals exhibited reduced MHC class II and CD83 expression but increased levels of CD80 and CD86 both before and during EAE. MOG-treated APC from LPS-exposed animals stimulated less T lymphocyte proliferation but increased expansion of CD4+FoxP3+ T cells compared with APC from PBS-exposed animals. Neuropathological studies disclosed reduced myelin and axonal loss in spinal cords from LPS-exposed compared with PBS-exposed animals with EAE, and this neuroprotective effect was associated with an increased number of CD3+FoxP3+ immunoreactive cells. Analyses of human brain tissue revealed that FoxP3 expression was detected in lymphocytes, albeit reduced in MS compared with non-MS patients’ brains. These findings support the concept of early-life microbial exposure influencing the generation of neuroprotective regulatory T cells and may provide insights into new immunotherapeutic strategies for MS.

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“…For many long years, the hygiene hypothesis was the accepted explanation for the characteristic feature of MS that this disorder is less prevalent in developing than in developed countries, and as regards the latter, its prevalence is higher in northern countries with better hygienic conditions than in the south or in the southern states of the United States. Early, pertinent studies were published from Israel during the sixties of the last century [4]. Surveys conducted in the United States, and internationally on immigrants relocating from countries with a high risk to countries with a low risk of MS or vice versa yielded very interesting findings [5].…”

Section: Epidemiological and Seroepidemiological Evidencementioning

confidence: 99%

The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders — Similarities and differences

Füst¹

2011

European Journal of Microbiology and Immunology

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After a brief summary on the properties of the Epstein-Barr virus (EBV), the course and latency stages of the infection, the characteristics of infectious mononucleosis (IM), and other disorders caused by this virus, as well as the course of the serological responses to EBV, the current paper focuses on the role of EBV in two autoimmune disorders: multiple sclerosis (MS), and systemic lupus erythematosus (SLE). Diverse evidence suggests that infection by EBV during late childhood or young adulthood may have a role in the pathogenesis of MS. These include the similarity between the geographical distribution of IM and MS, the high risk of contracting MS by individuals who have recovered from IM, the elevation of the titers of IgG antibodies against EBV nuclear antigens occurring years before the initial manifestations of MS, and the extremely rare occurrence of MS in individuals seronegative for EBV. However, the data on the mechanism underlying the relationship between EBV and MS are controversial. Moreover, many observations indicate that EBV contributes also to the pathomechanism of SLE. However, this contribution differs from the relationship between EBV and MS, as shown by the lack of any increase in the risk of SLE after IM. In SLE, EBV serology is quantitatively and qualitatively different from the normal response -that is, EBV viral load is higher and a strong cross-reaction can be detected between certain EBV antigens and autoantigens of pathological importance. These observations, along with the findings pointing to a possible role of EBV in rheumatoid arthritis and myasthenia gravis indicate that infection by EBV may be one of the environmental factors, which can facilitate the development of some autoimmune disorders in genetically susceptible individuals.

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Epidemiological study of multiple sclerosis in Israel. II. Multiple sclerosis and level of sanitation.

Cited by 146 publications

References 24 publications

Epstein-Barr virus and multiple sclerosis: interaction with HLA

Epstein-Barr virus and multiple sclerosis: interaction with HLA

Early Life Exposure to Lipopolysaccharide Suppresses Experimental Autoimmune Encephalomyelitis by Promoting Tolerogenic Dendritic Cells and Regulatory T Cells

The role of the Epstein-Barr virus in the pathogenesis of some autoimmune disorders — Similarities and differences

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