HLA-DRB1*15 allele influences the later course of relapsing remitting multiple sclerosis

Cournu-Rebeix, Isabelle; Génin, Emmanuelle; Leray, Emmanuelle; Babron, Marie‐Claude; Cohen, Jérémie F.; Gout, C.; Alizadeh, Mehdi; Perdry, Hervé; Sémana, G.; Brassat, David; Clerget‐Darpoux, Françoise; Yaouanq, J.; Edan, Gilles; Rosenheim, M.; Fontaine, Bertrand

doi:10.1038/gene.2008.52

Cited by 25 publications

(20 citation statements)

References 25 publications

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“…Epitope spread has been suggested to be the cause of relapse in other relapsing-remitting models of EAE (9, 10, 35) and both initiation and progression of epitope spread are strongly dependent upon MHC class II haplotype in animal models and patients (7, 25, 36-38). Further, intra- and intermolecular epitope spread have been demonstrated in the context of IA g7 in the autoimmune diabetes model in NOD mice (2, 3).…”

Section: Discussionmentioning

confidence: 99%

Progression of Relapsing-Remitting Demyelinating Disease Does Not Require Increased TCR Affinity or Epitope Spread

Kersh

Edwards

Evavold

2014

The Journal of Immunology

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In this study, we investigate the basis of T cell recognition of myelin that governs the progression from acute symptoms into disease remission, relapse and chronic progression in a secondary progressive model of demyelinating disease. Until now, the frequency and affinity of myelin-reactive CD4 T cells that elicit relapsing-remitting disease have not been quantified. The micropipette adhesion frequency assay was used to obtain a sensitive and physiologically relevant two-dimensional measurement of frequency and TCR affinity for myelin, as the inherent low affinity does not allow the use of specific-peptide:MHC-II tetramers for this purpose. We found the highest affinity and frequency of polyclonal myelin oligodendrocyte glycoprotein (MOG)-reactive cells infiltrate the CNS during acute disease, while affinities during remission, relapse and chronic disease are not significantly different from each other. Frequency analysis revealed that the vast majority of CNS-infiltrating CD4 T cells are MOG-reactive at all time points demonstrating epitope spread is not a predominant factor for disease progression. Further, time points at which mice were symptomatic were characterized by an infiltration of Th17 cells in the CNS while symptom remission showed an enrichment of cells producing IFN-γ. Also, the ratio of regulatory T cells to Foxp3- CD4 T cells was significantly higher in the CNS at remission than during acute disease. The results of this study indicate that a high frequency of T cells specific for a single myelin antigen, rather than increased TCR affinity or epitope spread, govern the transition from acute symptoms through remission, relapse and chronic disease states.

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Section: Discussionmentioning

confidence: 99%

Progression of Relapsing-Remitting Demyelinating Disease Does Not Require Increased TCR Affinity or Epitope Spread

Kersh

Edwards

Evavold

2014

The Journal of Immunology

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“…Although several previous studies had not found any relationship between DRB1*15 and disease severity [21,33], recent studies in different populations did find it related with a worse prognosis [32,34,35]. The results of a recent research suggest that the DRB1*1501 allele increases the disease severity by facilitating the development of T2 lesions in MRI [36].…”

Section: Discussionmentioning

confidence: 89%

Epistasis between HLA-DRB1 parental alleles in a Spanish cohort with multiple sclerosis

Romero-Pinel

Pujal

Martínez-Yélamos

et al. 2010

Journal of the Neurological Sciences

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“…MS French family trios were prospectively recruited as part of a survey of MS patients identified throughout France by REFGENSEP, the French MS Genetics Group [24]. Trios were ascertained through one patient (child) per family and two parents available for typing.…”

Section: Methodsmentioning

confidence: 99%

Prenatal Vitamin D Deficiency Induces an Early and More Severe Experimental Autoimmune Encephalomyelitis in the Second Generation

Abreu

Landel

Barnett

et al. 2012

IJMS

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In a previous study, we demonstrated that mouse adult F1 offspring, exposed to a vitamin D deficiency during pregnancy, developed a less severe and delayed Experimental Autoimmune Encephalomyelitis (EAE), when compared with control offspring. We then wondered whether a similar response was observed in the subsequent generation. To answer this question, we assessed F2 females whose F1 parents (males or females) were vitamin D-deprived when developing in the uterus of F0 females. Unexpectedly, we observed that the vitamin D deficiency affecting the F0 pregnant mice induced a precocious and more severe EAE in the F2 generation. This paradoxical finding led us to assess its implications for the epidemiology of Multiple Sclerosis (MS) in humans. Using the REFGENSEP database for MS trios (the patient and his/her parents), we collected the parents’ dates of birth and assessed a potential season of birth effect that could potentially be indicative of the vitamin D status of the pregnant grandmothers. A trend for a reduced number of births in the Fall for the parents of MS patients was observed but statistical significance was not reached. Further well powered studies are warranted to validate the latter finding.

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HLA-DRB1*15 allele influences the later course of relapsing remitting multiple sclerosis

Cited by 25 publications

References 25 publications

Progression of Relapsing-Remitting Demyelinating Disease Does Not Require Increased TCR Affinity or Epitope Spread

Progression of Relapsing-Remitting Demyelinating Disease Does Not Require Increased TCR Affinity or Epitope Spread

Epistasis between HLA-DRB1 parental alleles in a Spanish cohort with multiple sclerosis

Prenatal Vitamin D Deficiency Induces an Early and More Severe Experimental Autoimmune Encephalomyelitis in the Second Generation

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