Systemic and local expression levels of TNF‐like ligand 1A and its decoy receptor 3 are increased in primary biliary cirrhosis

Abstract Background & Aims Through a genome‐wide association study of a Japanese population, we recently identified TNFSF 15 , a gene encoding TNF ‐like ligand 1A ( TL 1A), as a susceptibility gene for primary biliary cirrhosis ( PBC ). We investigated the clinical significance of TL 1A and one of its receptors, decoy receptor 3 (DcR3), in PBC . Methods We analysed the systemic and local expression of TL 1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme‐linked immunosorbent assay, quantitative polymerase chain reaction and immunohistochemical staining. Results Serum TL 1A 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. TL 1A was immunohistochemically localized to biliary epithelial cells, Kupffer cells, blood vessels and infiltrating mononuclear cells in the PBC liver. In addition, TL 1A 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. Conclusions These results indicate that TL 1A and DcR3 may play an important role in the pathogenesis of PBC .