• Yoshihiro Aiba, Kenichi Harada, Atsumasa Komori, Masahiro Ito, Shinji Shimoda, Hitomi Nakamura, Shinya Nagaoka, Seigo Abiru, Kiyoshi Migita, Hiromi Ishibashi, Yasuni Nakanuma, Nao Nishida, Minae Kawashima, Katsushi Tokunaga, Hiroshi Yatsuhashi, and Minoru Nakamura.
• Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
• Liver Int. 2014 May 1; 34 (5): 679-88.

Background & AimsThrough a genome-wide association study of a Japanese population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We investigated the clinical significance of TL1A and one of its receptors, decoy receptor 3 (DcR3), in PBC.MethodsWe analysed the systemic and local expression of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining.ResultsSerum TL1A levels were significantly increased in PBC patients at both early and late stages as compared with healthy controls, and its levels were significantly decreased in early-stage PBC patients after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA expression was increased in the PBC liver as compared with the non-diseased liver. Serum DcR3 levels were also significantly increased in PBC patients, and were significantly decreased after UDCA treatment in early-stage PBC patients.ConclusionsThese results indicate that TL1A and DcR3 may play an important role in the pathogenesis of PBC.© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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