{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:41:15Z","timestamp":1789990875964,"version":"4.0.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2009,8,20]],"date-time":"2009-08-20T00:00:00Z","timestamp":1250726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2009,8,20]],"date-time":"2009-08-20T00:00:00Z","timestamp":1250726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Immun"],"published-print":{"date-parts":[[2009,12]]},"DOI":"10.1038\/gene.2009.64","type":"journal-article","created":{"date-parts":[[2009,8,20]],"date-time":"2009-08-20T09:01:06Z","timestamp":1250758866000},"page":"667-672","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["The PTPN22gain-of-function+1858T(+) genotypes correlate with low IL-2 expression in thymomas and predispose to myasthenia gravis"],"prefix":"10.1038","volume":"10","author":[{"given":"W-Y","family":"Chuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Str\u00f6bel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Belharazem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Rieckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K V","family":"Toyka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Nix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Schalke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Kiefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Klinker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Opitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T-t","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H K","family":"M\u00fcller-Hermelink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Marx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,8,20]]},"reference":[{"key":"BFgene200964_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1196\/annals.1254.025","volume":"998","author":"A Marx","year":"2003","unstructured":"Marx A, M\u00fcller-Hermelink HK, Str\u00f6bel P . The role of thymomas in the development of myasthenia gravis. Ann N Y Acad Sci 2003; 998: 223\u2013236.","journal-title":"Ann N Y Acad Sci"},{"key":"BFgene200964_CR2","first-page":"447","volume":"127","author":"N Willcox","year":"1987","unstructured":"Willcox N, Schluep M, Ritter MA, Schuurman HJ, Newsom-Davis J, Christensson B . Myasthenic and non-myasthenic thymoma. An expansion of a minor cortical epithelial cell subset? Am J Pathol 1987; 127: 447\u2013460.","journal-title":"Am J Pathol"},{"key":"BFgene200964_CR3","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1002\/path.2141","volume":"211","author":"P Str\u00f6bel","year":"2007","unstructured":"Str\u00f6bel P, Murum\u00e4gi A, Klein R, Luster M, Lahti M, Krohn K et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J Pathol 2007; 211: 563\u2013571.","journal-title":"J Pathol"},{"key":"BFgene200964_CR4","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1002\/ana.20577","volume":"58","author":"WY Chuang","year":"2005","unstructured":"Chuang WY, Str\u00f6bel P, Gold R, Nix W, Schalke B, Kiefer R et al. A CTLA4high genotype is associated with myasthenia gravis in thymoma patients. Ann Neurol 2005; 58: 644\u2013648.","journal-title":"Ann Neurol"},{"key":"BFgene200964_CR5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/ng1323","volume":"36","author":"N Bottini","year":"2004","unstructured":"Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004; 36: 337\u2013338.","journal-title":"Nat Genet"},{"key":"BFgene200964_CR6","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1086\/429096","volume":"76","author":"LA Criswell","year":"2005","unstructured":"Criswell LA, Pfeiffer KA, Lum RF, Gonzales B, Novitzke J, Kern M et al. Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am J Hum Genet 2005; 76: 561\u2013571.","journal-title":"Am J Hum Genet"},{"key":"BFgene200964_CR7","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.2337\/diabetes.53.11.3020","volume":"53","author":"D Smyth","year":"2004","unstructured":"Smyth D, Cooper JD, Collins JE, Heward JM, Franklyn JA, Howson JM et al. Replication of an association between the lymphoid tyrosine phosphatase locus (LYP\/PTPN22) with type 1 diabetes, and evidence for its role as a general autoimmunity locus. Diabetes 2004; 53: 3020\u20133023.","journal-title":"Diabetes"},{"key":"BFgene200964_CR8","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1038\/nature01621","volume":"423","author":"H Ueda","year":"2003","unstructured":"Ueda H, Howson JM, Esposito L, Heward J, Snook H, Chamberlain G et al. Association of the T-cell regulatory gene CTLA4 with susceptibility to autoimmune disease. Nature 2003; 423: 506\u2013511.","journal-title":"Nature"},{"key":"BFgene200964_CR9","doi-asserted-by":"publisher","first-page":"906","DOI":"10.2337\/diabetes.54.3.906","volume":"54","author":"W Zheng","year":"2005","unstructured":"Zheng W, She JX . Genetic association between a lymphoid tyrosine phosphatase (PTPN22) and type 1 diabetes. Diabetes 2005; 54: 906\u2013908.","journal-title":"Diabetes"},{"key":"BFgene200964_CR10","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1086\/423790","volume":"75","author":"C Kyogoku","year":"2004","unstructured":"Kyogoku C, Langefeld CD, Ortmann WA, Lee A, Selby S, Carlton VE et al. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet 2004; 75: 504\u2013507.","journal-title":"Am J Hum Genet"},{"key":"BFgene200964_CR11","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1073\/pnas.0610250104","volume":"104","author":"L Michou","year":"2007","unstructured":"Michou L, Lasbleiz S, Rat AC, Migliorini P, Balsa A, Westhovens R et al. Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene. Proc Natl Acad Sci USA 2007; 104: 1649\u20131654.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFgene200964_CR12","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1002\/ana.20751","volume":"59","author":"C Vandiedonck","year":"2006","unstructured":"Vandiedonck C, Capdevielle C, Giraud M, Krumeich S, Jais JP, Eymard B et al. Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis. Ann Neurol 2006; 59: 404\u2013407.","journal-title":"Ann Neurol"},{"key":"BFgene200964_CR13","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/rheumatology\/kel170","volume":"46","author":"YH Lee","year":"2007","unstructured":"Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK et al. The PTPN22 C1858T functional polymorphism and autoimmune diseases\u2014a meta-analysis. Rheumatology (Oxford) 2007; 46: 49\u201356.","journal-title":"Rheumatology (Oxford)"},{"key":"BFgene200964_CR14","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1038\/ng1673","volume":"37","author":"T Vang","year":"2005","unstructured":"Vang T, Congia M, Macis MD, Musumeci L, Orr\u00fa V, Zavattari P et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet 2005; 37: 1317\u20131319.","journal-title":"Nat Genet"},{"key":"BFgene200964_CR15","doi-asserted-by":"publisher","first-page":"5945","DOI":"10.4049\/jimmunol.166.10.5945","volume":"166","author":"H Bassiri","year":"2001","unstructured":"Bassiri H, Carding SR . A requirement for IL-2\/IL-2 receptor signaling in intrathymic negative selection. J Immunol 2001; 166: 5945\u20135954.","journal-title":"J Immunol"},{"key":"BFgene200964_CR16","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.jneuroim.2008.04.004","volume":"197","author":"AK Lefvert","year":"2008","unstructured":"Lefvert AK, Zhao Y, Ramanujam R, Yu S, Pirskanen R, Hammarstr\u00f6m L . PTPN22 R620W promotes production of anti-AChR autoantibodies and IL-2 in myasthenia gravis. J Neuroimmunol 2008; 197: 110\u2013113.","journal-title":"J Neuroimmunol"},{"key":"BFgene200964_CR17","doi-asserted-by":"publisher","first-page":"46478","DOI":"10.1074\/jbc.M206894200","volume":"277","author":"S Anjos","year":"2002","unstructured":"Anjos S, Nguyen A, Ounissi-Benkalha H, Tessier MC, Polychronakos C . A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. J Biol Chem 2002; 277: 46478\u201346486.","journal-title":"J Biol Chem"},{"key":"BFgene200964_CR18","doi-asserted-by":"publisher","first-page":"6606","DOI":"10.4049\/jimmunol.165.11.6606","volume":"165","author":"T Kouki","year":"2000","unstructured":"Kouki T, Sawai Y, Gardine CA, Fisfalen ME, Alegre ML, DeGroot LJ . CTLA-4 gene polymorphism at position 49 in exon 1 reduces the inhibitory function of CTLA-4 and contributes to the pathogenesis of Graves' disease. J Immunol 2000; 165: 6606\u20136611.","journal-title":"J Immunol"},{"key":"BFgene200964_CR19","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1182\/blood.V100.1.159","volume":"100","author":"P Str\u00f6bel","year":"2002","unstructured":"Str\u00f6bel P, Helmreich M, Menioudakis G, Lewin SR, R\u00fcdiger T, Bauer A et al. Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood 2002; 100: 159\u2013166.","journal-title":"Blood"},{"key":"BFgene200964_CR20","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/ana.1017","volume":"50","author":"C Buckley","year":"2001","unstructured":"Buckley C, Douek D, Newsom-Davis J, Vincent A, Willcox N . Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann Neurol 2001; 50: 64\u201372.","journal-title":"Ann Neurol"},{"key":"BFgene200964_CR21","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1182\/blood.V96.12.3872","volume":"96","author":"V Hoffacker","year":"2000","unstructured":"Hoffacker V, Schultz A, Tiesinga JJ, Gold R, Schalke B, Nix W et al. Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 2000; 96: 3872\u20133879.","journal-title":"Blood"},{"key":"BFgene200964_CR22","doi-asserted-by":"publisher","first-page":"5421","DOI":"10.4049\/jimmunol.170.11.5421","volume":"170","author":"JE Buhlmann","year":"2003","unstructured":"Buhlmann JE, Elkin SK, Sharpe AH . A role for the B7-1\/B7-2:CD28\/CTLA-4 pathway during negative selection. J Immunol 2003; 170: 5421\u20135428.","journal-title":"J Immunol"},{"key":"BFgene200964_CR23","doi-asserted-by":"publisher","first-page":"6645","DOI":"10.4049\/jimmunol.173.11.6645","volume":"173","author":"H Kwon","year":"2004","unstructured":"Kwon H, Jun HS, Khil LY, Yoon JW . Role of CTLA-4 in the activation of single- and double-positive thymocytes. J Immunol 2004; 173: 6645\u20136653.","journal-title":"J Immunol"},{"key":"BFgene200964_CR24","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1128\/MCB.12.5.2396","volume":"12","author":"RJ Matthews","year":"1992","unstructured":"Matthews RJ, Bowne DB, Flores E, Thomas ML . Characterization of hematopoietic intracellular protein tyrosine phosphatases: description of a phosphatase containing an SH2 domain and another enriched in proline-, glutamic acid-, serine-, and threonine-rich sequences. Mol Cell Biol 1992; 12: 2396\u20132405.","journal-title":"Mol Cell Biol"},{"key":"BFgene200964_CR25","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1182\/blood.V93.6.2013.406k25_2013_2024","volume":"93","author":"S Cohen","year":"1999","unstructured":"Cohen S, Dadi H, Shaoul E, Sharfe N, Roifman CM . Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood 1999; 93: 2013\u20132024.","journal-title":"Blood"},{"key":"BFgene200964_CR26","doi-asserted-by":"publisher","first-page":"11002","DOI":"10.1074\/jbc.M600498200","volume":"281","author":"J Wu","year":"2006","unstructured":"Wu J, Katrekar A, Honigberg LA, Smith AM, Conn MT, Tang J et al. Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem 2006; 281: 11002\u201311010.","journal-title":"J Biol Chem"},{"key":"BFgene200964_CR27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/BF02899268","volume":"63","author":"F Fend","year":"1993","unstructured":"Fend F, Kirchner T, Marx A, M\u00fcller-Hermelink HK . B-cells in thymic epithelial tumours. An immunohistochemical analysis of intra- and extraepithelial B-cells. Virchows Arch B Cell Pathol Incl Mol Pathol 1993; 63: 241\u2013247.","journal-title":"Virchows Arch B Cell Pathol Incl Mol Pathol"},{"key":"BFgene200964_CR28","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/nature06066","volume":"448","author":"M Giraud","year":"2007","unstructured":"Giraud M, Taubert R, Vandiedonck C, Ke X, L\u00e9vi-Strauss M, Pagani F et al. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature 2007; 448: 934\u2013937.","journal-title":"Nature"}],"container-title":["Genes & Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/gene200964.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gene200964","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/gene200964.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T16:15:16Z","timestamp":1647965716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/gene200964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,20]]},"references-count":28,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["BFgene200964"],"URL":"https:\/\/doi.org\/10.1038\/gene.2009.64","relation":{},"ISSN":["1466-4879","1476-5470"],"issn-type":[{"value":"1466-4879","type":"print"},{"value":"1476-5470","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,20]]},"assertion":[{"value":"23 February 2009","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2009","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2009","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2009","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}