{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T02:01:08Z","timestamp":1774663268509,"version":"3.50.1"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,11,17]],"date-time":"2005-11-17T00:00:00Z","timestamp":1132185600000},"content-version":"vor","delay-in-days":3364,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Celiac disease (CD) is an immune disease triggered by the cereal antigen gliadin, resulting in villous atrophy in the small intestine. Susceptibility to the development of CD is strongly influenced by genes in the major histocompatibility complex, in particular alleles of the DQ genes in the class II region. However recent evidence has suggested that the major histocompatibility complex (MHC) class III region may be linked to celiac disease independently of the class II region. Among the genes located in this area is <jats:italic>TNF<\/jats:italic>\u2010\u03b1, which encodes the cytokine tumor necrosis factor\u2010\u03b1 which has a broad range of pro\u2010inflammatory, immunomodulatory and catabolic activities. Therefore, aberrant expression of <jats:italic>TNF<\/jats:italic>\u2010\u03b1 could be important in the pathogenesis of MHC\u2010associated immune disorders. A <jats:italic>TNF<\/jats:italic>\u2010\u03b1 variant with a polymorphism in its promoter region has been described and designated <jats:italic>TNF2<\/jats:italic>. <jats:italic>TNF2<\/jats:italic> has been associated with a variety of MHC\u2010linked diseases, including systemic lupus erythematosus, dermatitis herpetiformis and insulin\u2010dependent diabetes mellitus (IDDM), as well as parasitic infections. <jats:italic>TNF2<\/jats:italic> has previously been shown to be associated with the MHC haplotype <jats:italic>HLAA1\u2010B8\u2010DR3\u2010DQ2<\/jats:italic>, which confers susceptibility to CD. We have analyzed the distribution of <jats:italic>TNF2<\/jats:italic> alleles in a group of celiac patients (<jats:italic>n<\/jats:italic> = 52) compared to controls (<jats:italic>n<\/jats:italic> = 52) in an effort to evaluate its role, if any, in susceptibility to the condition. <jats:italic>TNF2<\/jats:italic> has a frequency of 0.5000 (SE \u00b1 0.0490) in CD, compared to 0.1635 (\u00b1 0.0362) in a control sample (<jats:italic>p<\/jats:italic> &lt; 10<jats:sup>\u22126<\/jats:sup>). Of 52 patients, 44 carried one or more <jats:italic>TNF2<\/jats:italic> alleles. Analysis indicates that the distribution of <jats:italic>TNF2<\/jats:italic> is best explained by assuming 100% allelic association between it and <jats:italic>HLA\u2010DQB1*0201<\/jats:italic> (frequency = 0.7791 \u00b1 0.0447). However, the number of <jats:italic>TNF2<\/jats:italic> heterozygotes significantly exceeds expectations and measurements of linkage disequilibrium confirm that allelic associations spanning the DQ and TNF regions are strongly maintained in CD. Taken together, these results indicate that <jats:italic>TNF2<\/jats:italic> may have a role in the pathogenesis of CD; however, since it is not an independent association, the possibility that <jats:italic>TNF2<\/jats:italic> constitutes a passive component of the CD haplotype cannot be excluded.<\/jats:p>","DOI":"10.1002\/eji.1830260923","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T02:34:16Z","timestamp":1172802856000},"page":"2113-2118","source":"Crossref","is-referenced-by-count":70,"title":["TNF2, a polymorphism of the tumour necrosis\u2010\u03b1 gene promoter, is a component of the celiac disease major histocompatibility complex haplotype"],"prefix":"10.1002","volume":"26","author":[{"given":"Ross","family":"Mc Manus","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony G.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald G.","family":"Weir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon W.","family":"Duff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dermot","family":"Kelleher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,17]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511570261.006"},{"key":"e_1_2_1_3_2","first-page":"S1","volume":"165","author":"Johnston S. 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