{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363388846331451008.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/ana.20514"}},{"identifier":{"@type":"URI","@value":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fana.20514"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.20514"}}],"dc:title":[{"@value":"A PD‐1 polymorphism is associated with disease progression in multiple sclerosis"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:p>T cells are considered to play a pivotal role in orchestrating the self‐reactive immune responses in multiple sclerosis (MS). Programmed death 1 (PD‐1) is a member of the B7/CD28 superfamily of costimulatory molecules exerting inhibitory functions on T cells. Recently, an intronic 7146G/A polymorphism within the PD‐1 gene was described and suggested to be associated with autoimmunity. We investigated whether this genetic polymorphism is a genetic modifier for risk and progression of MS. Blood samples from 939 German MS patients (mean age, 39 years; range, 13–71; 566 patients [60%] with relapsing‐remitting MS, 279 (30%) with secondary, and 94 (10%) with primary progressive MS) and 272 healthy white controls were tested. Genotyping was performed by polymerase chain reaction and restriction enzyme digestion; results were confirmed by automatic sequencing. A significant association of the mutated allele with a progressive disease course was detected (44% 7146G vs 56% 7146A, χ<jats:sup>2</jats:sup> <jats:italic>p</jats:italic> = 0.002). Consequences of the PD‐1 mutation for T‐cell function were assessed ex vivo in some patients using microsphere‐stimulated peripheral blood lymphocytes and purified CD4 cells. Importantly, PD‐1–mediated inhibition of T‐cell cytokine secretion (interferon‐γ) is impaired in patients carrying the PD‐1 polymorphism. In conclusion, our data suggest that PD‐1 polymorphism is a genetic modifier of the progression of MS, possibly through inducing a partial defect in PD‐1–mediated inhibition of T‐cell activation. Ann Neurol 2005</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383388846331451011","@type":"Researcher","foaf:name":[{"@value":"Antje Kroner"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846331451009","@type":"Researcher","foaf:name":[{"@value":"Matthias Mehling"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846331451010","@type":"Researcher","foaf:name":[{"@value":"Bernhard Hemmer"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846331451008","@type":"Researcher","foaf:name":[{"@value":"Peter Rieckmann"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846331451013","@type":"Researcher","foaf:name":[{"@value":"Klaus V. Toyka"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846331451012","@type":"Researcher","foaf:name":[{"@value":"Mathias Mäurer"}]},{"@id":"https://cir.nii.ac.jp/crid/1383388846331451014","@type":"Researcher","foaf:name":[{"@value":"Heinz Wiendl"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"03645134"},{"@type":"EISSN","@value":"15318249"}],"prism:publicationName":[{"@value":"Annals of Neurology"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2005-05-23","prism:volume":"58","prism:number":"1","prism:startingPage":"50","prism:endingPage":"57"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fana.20514"},{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.20514"}],"createdAt":"2005-05-24","modifiedAt":"2023-10-16","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050282810754542848","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Programmed cell death 1 inhibits inflammatory helper T-cell development through controlling the innate immune response"}]},{"@id":"https://cir.nii.ac.jp/crid/1050294045367952640","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Transcription Factor c-Maf Promotes Immunoregulation of Programmed Cell Death 1–Expressed CD8+ T Cells in Multiple Sclerosis"},{"@value":"Transcription Factor c-Maf Promotes Immunoregulation of Programmed Cell Death 1–Expressed CD8\n            <sup>+</sup>\n            T Cells in Multiple Sclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380140906112","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Programmed cell death-1-modified pig developed using electroporation-mediated gene editing for in vitro fertilized zygotes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848660423456384","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Dysregulated T cells in multiple sclerosis"}]},{"@id":"https://cir.nii.ac.jp/crid/1361412889843667968","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Role of PD-1 in Immunity and Diseases"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1002/ana.20514"},{"@type":"CROSSREF","@value":"10.1073/pnas.1315828110_references_DOI_2MVREyKY6ouUmRYdvsDcmLKx0Ow"},{"@type":"CROSSREF","@value":"10.1007/s11626-024-00869-4_references_DOI_2MVREyKY6ouUmRYdvsDcmLKx0Ow"},{"@type":"CROSSREF","@value":"10.1111/cen3.12438_references_DOI_2MVREyKY6ouUmRYdvsDcmLKx0Ow"},{"@type":"CROSSREF","@value":"10.1212/nxi.0000000000001166_references_DOI_2MVREyKY6ouUmRYdvsDcmLKx0Ow"},{"@type":"CROSSREF","@value":"10.1007/82_2017_67_references_DOI_2MVREyKY6ouUmRYdvsDcmLKx0Ow"}]}