{"@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/1361699995768899072.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1002/art.21575"}},{"identifier":{"@type":"URI","@value":"http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fart.21575"}},{"identifier":{"@type":"URI","@value":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.21575"}}],"dc:title":[{"@value":"A new model for an etiology of rheumatoid arthritis: Smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullination"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n                  <jats:sec>\n                    <jats:title>Objective</jats:title>\n                    <jats:p>To investigate whether smoking and HLA–DR shared epitope (SE) genes may interact in triggering immune reactions to citrulline‐modified proteins.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods</jats:title>\n                    <jats:p>In a case–control study involving patients with recent‐onset rheumatoid arthritis (RA), we studied interactions between a major environmental risk factor (smoking), major susceptibility genes included in the SE of HLA–DR, and the presence of the most specific autoimmunity known for RA (i.e., antibodies to proteins modified by citrullination). Immunostaining for citrullinated proteins in cells from bronchoalveolar lavage fluid was used to investigate whether smoking is associated with citrullination in the lungs.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results</jats:title>\n                    <jats:p>Previous smoking was dose‐dependently associated with occurrence of anticitrulline antibodies in RA patients. The presence of SE genes was a risk factor only for anticitrulline‐positive RA, and not for anticitrulline‐negative RA. A major gene–environment interaction between smoking and HLA–DR SE genes was evident for anticitrulline‐positive RA, but not for anticitrulline‐negative RA, and the combination of smoking history and the presence of double copies of HLA–DR SE genes increased the risk for RA 21‐fold compared with the risk among nonsmokers carrying no SE genes. Positive immunostaining for citrullinated proteins was recorded in bronchoalveolar lavage cells from smokers but not in those from nonsmokers.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion</jats:title>\n                    <jats:p>We identified an environmental factor, smoking, that in the context of HLA–DR SE genes may trigger RA‐specific immune reactions to citrullinated proteins. These data thus suggest an etiology involving a specific genotype, an environmental provocation, and the induction of specific autoimmunity, all restricted to a distinct subset of RA.</jats:p>\n                  </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381699995768899072","@type":"Researcher","foaf:name":[{"@value":"Lars Klareskog"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899082","@type":"Researcher","foaf:name":[{"@value":"Patrik Stolt"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899074","@type":"Researcher","foaf:name":[{"@value":"Karin Lundberg"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768898945","@type":"Researcher","foaf:name":[{"@value":"Henrik Källberg"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899078","@type":"Researcher","foaf:name":[{"@value":"Camilla Bengtsson"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899075","@type":"Researcher","foaf:name":[{"@value":"Johan Grunewald"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899076","@type":"Researcher","foaf:name":[{"@value":"Johan Rönnelid"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899079","@type":"Researcher","foaf:name":[{"@value":"Helena Erlandsson Harris"}]},{"@id":"https://cir.nii.ac.jp/crid/1380861292192313984","@type":"Researcher","foaf:name":[{"@value":"Ann‐Kristin Ulfgren"}]},{"@id":"https://cir.nii.ac.jp/crid/1380861292192313985","@type":"Researcher","foaf:name":[{"@value":"Solbritt Rantapää‐Dahlqvist"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768898944","@type":"Researcher","foaf:name":[{"@value":"Anders Eklund"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899073","@type":"Researcher","foaf:name":[{"@value":"Leonid Padyukov"}]},{"@id":"https://cir.nii.ac.jp/crid/1381699995768899081","@type":"Researcher","foaf:name":[{"@value":"Lars Alfredsson"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00043591"},{"@type":"EISSN","@value":"15290131"},{"@type":"PISSN","@value":"http://id.crossref.org/issn/00043591"}],"prism:publicationName":[{"@value":"Arthritis & Rheumatism"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2005-12-29","prism:volume":"54","prism:number":"1","prism:startingPage":"38","prism:endingPage":"46"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"http://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fart.21575"},{"@id":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.21575"}],"createdAt":"2005-12-29","modifiedAt":"2023-10-10","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050282677602602624","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Association between Anti-Ganglionic Nicotinic Acetylcholine Receptor (gAChR) Antibodies and HLA-DRB1 Alleles in the Japanese Population"}]},{"@id":"https://cir.nii.ac.jp/crid/1050564285764256128","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study."}]},{"@id":"https://cir.nii.ac.jp/crid/1360283689371268480","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Effects of Smoking and Shared Epitope on the Production of Anti–Citrullinated Peptide Antibody in a Japanese Adult Population"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285710468958720","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Anti-citrullinated glucose-6-phosphate isomerase peptide antibodies in patients with rheumatoid arthritis are associated with <i>HLA-DRB1</i> shared epitope alleles and disease activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285711825132544","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Respiratory mechanics measured by forced oscillation technique in rheumatoid arthritis-related pulmonary abnormalities: frequency-dependence, heterogeneity and effects of smoking"}]},{"@id":"https://cir.nii.ac.jp/crid/1360285714858710528","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Cutting Edge: B Cells Expressing Cyclic Citrullinated Peptide–Specific Antigen Receptor Are Tolerized in Normal Conditions"}]},{"@id":"https://cir.nii.ac.jp/crid/1360294643812644480","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Antigen-driven autoantibody production in lungs of interstitial lung disease with autoimmune disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565167315067392","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The role and therapeutic targeting of IL-6 in rheumatoid arthritis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567181954502400","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Genetic basis of rheumatoid arthritis: A current review"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588381048031360","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Identification of citrullinated α1-antitrypsin (A1AT) in saliva in a mouse model of rheumatoid arthritis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360849945982999680","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Shared epitope defines distinct associations of cigarette smoking with levels of anticitrullinated protein antibody and rheumatoid factor"}]},{"@id":"https://cir.nii.ac.jp/crid/1361699993439229824","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"PADI4 polymorphism predisposes male smokers to rheumatoid arthritis"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205258414720","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Novel anti-citrullinated peptide autoantibodies identified by proteomics with in vitro citrullinated proteins in patients with rheumatoid arthritis"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001205482585728","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"第2回関節リウマチとHLA"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679124688256","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Genetic studies of rheumatoid arthritis"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679218110080","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Anti-Cyclic Citrullinated Peptide Antibodies in Rheumatoid Arthritis and Behcet's Disease"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282681421321216","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"4. 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