{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:45:38Z","timestamp":1789076738568,"version":"build-2803163510"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2003,9,1]],"date-time":"2003-09-01T00:00:00Z","timestamp":1062374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although Abs to SSA\/Ro-SSB\/La are necessary for the development of congenital heart block (CHB), the low frequency suggests that fetal factors are contributory. Because CHB involves a cascade from inflammation to scarring, polymorphisms of the TNF-\u03b1 promoter region and codons 10 and 25 of the TGF-\u03b2 gene were evaluated in 88 children (40 CHB, 17 rash, 31 unaffected siblings) and 74 mothers from the Research Registry for Neonatal Lupus (NL). Cytokine expression was assessed in autopsy material from two fetuses with CHB. Significantly increased frequency of the \u2212308A (high-producer) allele of TNF-\u03b1 was observed in all NL groups compared with controls. In contrast, the TGF-\u03b2 polymorphism Leu10 (associated with increased fibrosis) was significantly higher in CHB children (genotypic frequency 60%, allelic frequency 78%) than unaffected offspring (genotypic frequency 29%, p = 0.016; allelic frequency 56%, p = 0.011) and controls, while there were no significant differences between controls and other NL groups. For the TGF-\u03b2 polymorphism, Arg25, there were no significant differences between NL groups and controls. In fetal CHB hearts, protein expression of TGF-\u03b2, but not TNF-\u03b1, was demonstrated in septal regions, extracellularly in the fibrous matrix, and intracellularly in macrophage infiltrates. Age-matched fetal hearts from voluntary terminations expressed neither cytokine. TNF-\u03b1 may be one of several factors that amplify susceptibility; however, the genetic studies, backed by the histological data, more convincingly link TGF-\u03b2 to the pathogenesis of CHB. This profibrosing cytokine and its secretion\/activation circuitry may provide a novel direction for evaluating fetal factors in the development of a robust animal model of CHB as well as therapeutic strategies in humans.<\/jats:p>","DOI":"10.4049\/jimmunol.171.6.3253","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T18:21:12Z","timestamp":1398018072000},"page":"3253-3261","source":"Crossref","is-referenced-by-count":86,"title":["Cytokine Polymorphisms and Histologic Expression in Autopsy Studies: Contribution of TNF-\u03b1 and TGF-\u03b21 to the Pathogenesis of Autoimmune-Associated Congenital Heart Block"],"prefix":"10.1093","volume":"171","author":[{"given":"Robert M","family":"Clancy","sequence":"first","affiliation":[{"name":"Hospital for Joint Diseases, New York University School of Medicine, Department of Rheumatology , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea B","family":"Backer","sequence":"additional","affiliation":[{"name":"Hospital for Joint Diseases, New York University School of Medicine, Department of Rheumatology , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Yin","sequence":"additional","affiliation":[{"name":"Hospital for Joint Diseases, New York University School of Medicine, Department of Rheumatology , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raj P","family":"Kapur","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital and Regional Medical Center, Department of Laboratories, and University of Washington , Seattle, WA 98105"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yair","family":"Molad","sequence":"additional","affiliation":[{"name":"Rabin Medical Center, Rheumatology Unit , Petah-Tikva ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill P","family":"Buyon","sequence":"additional","affiliation":[{"name":"Hospital for Joint Diseases, New York University School of Medicine, Department of Rheumatology , New York, NY 10003"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,9,15]]},"reference":[{"key":"2026020210240351000_R1","first-page":"544","volume-title":"Ann. 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