{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T08:59:00Z","timestamp":1778662740862,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T00:00:00Z","timestamp":1091664000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The precipitating event(s) that triggers Wegener's granulomatosis (WG) is unknown. Cytokines, costimulatory molecules, and counterregulatory molecules control the quality and intensity of immune responses. Thus, they are relevant candidates for genetic studies of immune dysregulation in WG, the pathogenesis of which may be facilitated by multiple acquired and\/or inherited factors. This study was undertaken to investigate possible genetic associations of various proinflammatory cytokines and CTLA\u20104, a receptor for T cell inhibition, with WG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using polymerase chain reaction\u2013based DNA genotyping, we investigated the polymorphisms located in the genes encoding a variety of proinflammatory cytokines and CTLA\u20104 in 117 American patients with WG and 123 ethnically matched healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with controls, patients with WG had a significantly lower frequency of homozygosity for the shortest allele (designated allele 86) of the <jats:italic>Ctla4<\/jats:italic> microsatellite polymorphism (AT)n located in the 3\u2032\u2010untranslated region (3\u2032\u2010UTR) of exon 3 (47.0% versus 69.9%; <jats:italic>P<\/jats:italic> = 0.0005). Significant differences between patients and controls in the allelic and genotypic frequencies of polymorphisms in the other cytokine and cytokine receptor genes studied (tumor necrosis factor \u03b1 [TNF\u03b1], TNF receptor I [TNFRI], TNFRII, interleukin\u20101\u03b2 [IL\u20101\u03b2], IL\u20106) were not found.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>Ctla4<\/jats:italic> (AT)n 86 allele has been previously demonstrated to be crucial for maintenance of normal levels of CTLA\u20104 expression and balance between T cell activation and inhibition. Our results in American patients confirm findings from a Scandinavian cohort in which a positive association between WG and longer alleles of (AT)n in the <jats:italic>Ctla4<\/jats:italic> 3\u2032\u2010UTR was demonstrated. Diminished frequencies of the most effective allele for CTLA\u20104 expression may represent a WG\u2010related susceptibility mutation that accounts, in part, for increased T cell activation and clonal expansion in WG. Blockade of T cell costimulation using CTLA\u20104Ig might be a useful therapeutic intervention, providing an alternative or complementary approach to conventional treatment with immunosuppressive agents.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20385","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T18:16:31Z","timestamp":1092075391000},"page":"2645-2650","source":"Crossref","is-referenced-by-count":50,"title":["An analysis of CTLA\u20104 and proinflammatory cytokine genes in Wegener's granulomatosis"],"prefix":"10.1002","volume":"50","author":[{"given":"Yihua","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DeRen","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pamela L.","family":"Paris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig 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