{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:58:39Z","timestamp":1792133919254,"version":"4.4.0"},"reference-count":15,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T00:00:00Z","timestamp":1219968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The C1858T polymorphism in <jats:italic>PTPN22<\/jats:italic> has been associated with the risk of systemic lupus erythematosus (SLE) as well as multiple other autoimmune diseases. We have previously shown that high serum interferon\u2010\u03b1 (IFN\u03b1) activity is a heritable risk factor for SLE. The aim of this study was to determine whether the <jats:italic>PTPN22<\/jats:italic> risk variant may shift serum cytokine profiles to higher IFN\u03b1 activity, resulting in risk of disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>IFN\u03b1 was measured in 143 patients with SLE, using a functional reporter cell assay, and tumor necrosis factor \u03b1 (TNF\u03b1) was measured by enzyme\u2010linked immunosorbent assay. The rs2476601 single\u2010nucleotide polymorphism in <jats:italic>PTPN22<\/jats:italic> (C1858T) was genotyped in the same patients. Patients were grouped, using a clustering algorithm, into 4 cytokine groups (IFN\u03b1 predominant, IFN\u03b1 and TNF\u03b1 correlated, TNF\u03b1 predominant, and both IFN\u03b1 and TNF\u03b1 low).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SLE patients carrying the risk allele of <jats:italic>PTPN22<\/jats:italic> had higher serum IFN\u03b1 activity than patients lacking the risk allele (<jats:italic>P<\/jats:italic> = 0.027). TNF\u03b1 levels were lower in carriers of the risk allele (<jats:italic>P<\/jats:italic> = 0.030), and the risk allele was more common in patients in the IFN\u03b1\u2010predominant and IFN\u03b1 and TNF\u03b1\u2010correlated groups as compared with patients in the TNF\u03b1\u2010predominant and both IFN\u03b1 and TNF\u03b1\u2010low groups (<jats:italic>P<\/jats:italic> = 0.001). Twenty\u2010five percent of male patients carried the risk allele, compared with 10% of female patients (<jats:italic>P<\/jats:italic> = 0.024); however, cytokine skewing was similar in both sexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The autoimmune disease risk allele of <jats:italic>PTPN22<\/jats:italic> is associated with skewing of serum cytokine profiles toward higher IFN\u03b1 activity and lower TNF\u03b1 levels in vivo in patients with SLE. This serum cytokine pattern may be relevant in other autoimmune diseases associated with the <jats:italic>PTPN22<\/jats:italic> risk allele.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.23728","type":"journal-article","created":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T20:46:07Z","timestamp":1220042767000},"page":"2818-2823","source":"Crossref","is-referenced-by-count":84,"title":["The <i>PTPN22<\/i> C1858T polymorphism is associated with skewing of cytokine profiles toward high interferon\u2010\u03b1 activity and low tumor necrosis factor \u03b1 levels in patients with lupus"],"prefix":"10.1002","volume":"58","author":[{"given":"Silvia N.","family":"Kariuki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Crow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Niewold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,8,29]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1064890"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197907053010102"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-004-1024-2"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364408"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel170"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21223"},{"issue":"9","key":"e_1_2_5_8_2","first-page":"S229","article-title":"Activation of the type I interferon pathway in autoimmune thyroid disease","volume":"56","author":"Mavragani CP","year":"2007","journal-title":"Arthritis Rheum"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200007)43:7<1431::AID-ANR3>3.0.CO;2-E"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408506102"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2004.01.008"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.7.4704"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23062"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0506-499"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1945"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23619"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.23728","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.23728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T23:22:11Z","timestamp":1696980131000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.23728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,8,29]]},"references-count":15,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1002\/art.23728"],"URL":"https:\/\/doi.org\/10.1002\/art.23728","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,29]]}}}