Genetic Epidemiology of Multiple Sclerosis

Sadovnick, A. Dessa; Dyment, D A; Ebers, G. C.

doi:10.1093/oxfordjournals.epirev.a017951

Cited by 58 publications

(51 citation statements)

References 32 publications

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“…is a chronic autoimmune disease of genetically susceptible hosts (1). Autoreactive T cells target constituents of myelin and oligodendrocytes for destruction, once a breach of the blood-brain barrier allows invasion by monocytes, dendritic cells, and effector T lymphocytes (2).…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice

Winer

Astsaturov

Cheung

et al. 2001

The Journal of Immunology

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Multiple sclerosis (MS) is a chronic autoimmune disease triggered by unknown environmental factors in genetically susceptible hosts. MS risk was linked to high rates of cow milk protein (CMP) consumption, reminiscent of a similar association in autoimmune diabetes. A recent rodent study showed that immune responses to the CMP, butyrophilin, can lead to encephalitis through antigenic mimicry with myelin oligodendrocyte glycoprotein. In this study, we show abnormal T cell immunity to several other CMPs in MS patients comparable to that in diabetics. Limited epitope mapping with the milk protein BSA identified one specific epitope, BSA193, which was targeted by most MS but not diabetes patients. BSA193 was encephalitogenic in SJL/J mice subjected to a standard protocol for the induction of experimental autoimmune encephalitis. These data extend the possible, immunological basis for the association of MS risk, CMP, and CNS autoimmunity. To pinpoint the same peptide, BSA193, in encephalitis-prone humans and rodents may imply a common endogenous ligand, targeted through antigenic mimicry.

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Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice

Winer

Astsaturov

Cheung

et al. 2001

The Journal of Immunology

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“…T ype I (insulin-dependent) diabetes mellitus and multiple sclerosis (MS) 4 are chronic, tissue-selective autoimmune diseases that reflect the interactions of polygenic traits with ill defined environmental factors (1,2). It is unknown what initiates and maintains autoimmunity to self-Ags expressed, respectively, in the pancreatic islets of Langerhans or CNS.…”

mentioning

confidence: 99%

Type I Diabetes and Multiple Sclerosis Patients Target Islet Plus Central Nervous System Autoantigens; Nonimmunized Nonobese Diabetic Mice Can Develop Autoimmune Encephalitis

Winer

Astsaturov

Cheung

et al. 2001

The Journal of Immunology

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Type I diabetes and multiple sclerosis (MS) are distinct autoimmune diseases where T cells target either islet or CNS self-proteins. Unexpectedly, we found that autoreactive T cells in diabetic patients, relatives with high diabetes risk, nonobese diabetic (NOD) mice, and MS patients routinely target classical islet as well as CNS autoantigens. The pathogenic potential of CNS autoreactivity was testable in NOD mice. Pertussis holotoxin, without additional Ags or adjuvants, allowed development of an NOD mouse-specific, autoimmune encephalitis with variable primary-progressive, monophasic, and relapsing-remitting courses. T cells from diabetic donors transferred CNS disease to pertussis toxin-pretreated NOD.scid mice, with accumulation of CD3/IFN-γ transcripts in the brain. Diabetes and MS appear more closely related than previously perceived. NOD mouse-specific, autoimmune encephalitis provides a new MS model to identify factors that determine alternative disease outcomes in hosts with similar autoreactive T cell repertoires.

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“…The genetic epidemiologic studies on MS have been extensive [Kuwert, 1977, Ebers et al, 1995Sadovnick et al, 1994Sadovnick et al, , 1997. The recurrence risk ratio Ï is approximately 20 for full sibs, 190 for MZ twins, and about 5.5 for second-degree relatives [Kuwert, 1977;Sadovnick, 1994Sadovnick, , 1997.…”

Section: Numerical Examplesmentioning

confidence: 99%

Gene-Environment Interaction and the Mapping of Complex Traits: Some Statistical Models and Their Implications

Guo¹

2000

Hum Hered

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The manifestation of many complex diseases or traits is very likely the result of an inextricable interplay of the biological and the environmental. Yet the role of environmental effect has traditionally been played down, for various reasons. In this paper, some simple statistical models that incorporate gene-environment interaction (GEI) have been proposed and their behavior and implications investigated. These implications concern the conditional independence assumption in likelihood calculation of pedigree data, the fine-tuning of the sib pair method for mapping quantitative traits, apportioning of disease or trait variation due to specific causes. In addition, they concern properties of gene mapping methods that do not take GEI into account, and they bring into question the utility of commonly used measures of genetic effects such as recurrence risk ratio for relative pairs, twin concordance rates, and heritability coefficients. In the presence of GEI, all these measures are functions not only of genetic effects and gene frequency, but also of environmental effects, the distribution of environmental factors in the population, and of GEI. Above all, these measures are all measures of familial aggregation, since they can be significant even in the absence of any genetic component of the disease. Thus their use as indicators of the genetic basis of complex diseases is cast into doubt.

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Genetic Epidemiology of Multiple Sclerosis

Cited by 58 publications

References 32 publications

T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice

T Cells of Multiple Sclerosis Patients Target a Common Environmental Peptide that Causes Encephalitis in Mice

Type I Diabetes and Multiple Sclerosis Patients Target Islet Plus Central Nervous System Autoantigens; Nonimmunized Nonobese Diabetic Mice Can Develop Autoimmune Encephalitis

Gene-Environment Interaction and the Mapping of Complex Traits: Some Statistical Models and Their Implications

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