Affiliation:
1. The University of Tokyo: Tokyo Daigaku
2. The Institute of Medical Science, Asahi Life Foundation
3. Saitama Medical University: Saitama Ika Daigaku
4. Juntendo University - Hongo Campus: Juntendo Daigaku
5. Saint Marianna University School of Medicine: Sei Marianna Ika Daigaku
Abstract
Abstract
Background and aims: There is a lack of biliary epithelial molecular markers for primary sclerosing cholangitis (PSC). We analyzed candidates from disease susceptibility genes identified in recent genome-wide association studies.
Methods: Expression was quantified using immunohistochemistry in biliary epithelia in liver biopsy samples from patients with PSC (N = 45) and controls (N = 12). Samples from patients with primary biliary cholangitis (PBC) were used as disease controls (N = 20).
Results: The levels of hepatic expression of ATXN2, HHEX, PRDX5, MST1, and TNFRSF14 were significantly altered in the PSC group. We focused on the immune-related receptor, TNFRSF14. Immunohistochemistry revealed that TNFRSF14 positivity was significantly higher in biliary epithelia in the PSC group (96 %) than in the control (42 %) and PBC (55 %) groups. High expression of TNFRSF14 was observed only in patients with PSC. Moreover, the expression of LIGHT, which encodes a TNFRSF14-activating ligand, was increased in PSC liver. Immunohistochemistry showed that high expression of LIGHT was more common in PSC biliary epithelia (53 %) than in the PBC (15 %) or control (0 %) groups; moreover, it was positively associated with fibrotic progression.
Conclusions: TNFRSF14 and LIGHT are attractive candidate markers for PSC.
Publisher
Research Square Platform LLC