{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T03:05:08Z","timestamp":1770433508319,"version":"3.49.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T00:00:00Z","timestamp":1181088000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T00:00:00Z","timestamp":1181088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>PTPN22<\/jats:italic> 1858C\/T polymorphism has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have shown that carriage of the T variant (CT or TT) of <jats:italic>PTPN22<\/jats:italic> in combination with anti-cyclic citrullinated peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA. In the present study we analysed the association between the <jats:italic>PTPN22<\/jats:italic> 1858C\/T polymorphism and early RA in patients from northern Sweden, related the polymorphism to autoantibodies and the HLA-DR shared epitope, and analysed their association with markers for disease activity and progression. The inception cohort includes individuals who also donated samples before disease onset. A case\u2013control study was performed in patients (<jats:italic>n<\/jats:italic> = 505; 342 females and 163 males) with early RA (mean duration of symptoms = 6.3 months) and in population-based matched controls (<jats:italic>n<\/jats:italic> = 970) from northern Sweden. Genotyping of the <jats:italic>PTPN22<\/jats:italic> 1858C\/T polymorphism was performed using a TaqMan instrument. HLA-shared epitope alleles were identified using PCR sequence-specific primers. Anti-CCP2 antibodies were determined using enzyme-linked immunoassays. Disease activity (that is, the number of swollen and tender joints, the global visual analogue scale, and the erythrocyte sedimentation rate) was followed on a regular basis (that is, at baseline and after 6, 12, 18 and 24 months). Both the 1858T allele and the carriage of T were associated with RA (\u03c7<jats:sup>2<\/jats:sup> = 23.84, P = 0.000001, odds ratio = 1.69, 95% confidence interval = 1.36\u20132.11; and \u03c7<jats:sup>2<\/jats:sup> = 22.68, P = 0.000002, odds ratio = 1.79, 95% confidence interval = 1.40\u20132.29, respectively). Association of the 1858T variant with RA was confined to seropositive disease. Carriage of 1858T and the presence of anti-CCP antibodies was independently associated with disease onset at an earlier age (P &lt; 0.05 and P &lt; 0.01, respectively), while the combination of both resulted in an even earlier age at onset. Smoking was identified as a risk factor independent of the 1858T variant and anti-CCP antibodies.<\/jats:p>","DOI":"10.1186\/ar2214","type":"journal-article","created":{"date-parts":[[2007,6,6]],"date-time":"2007-06-06T18:13:41Z","timestamp":1181153621000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["The PTPN221858C\/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden"],"prefix":"10.1186","volume":"9","author":[{"given":"Heidi","family":"Kokkonen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Innala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Jidell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solbritt","family":"Rantap\u00e4\u00e4-Dahlqvist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2007,6,6]]},"reference":[{"key":"2065_CR1","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1086\/422827","volume":"75","author":"AB Begovich","year":"2004","unstructured":"Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC, Ardlie KG, Huang Q, Smith AM, Spoerke JM, et al: A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. 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