Introduction

Primary sclerosing cholangitis (PSC) is an idiopathic cholestatic disease. Recent genome-wide studies (GWAS) have identified about 30 disease susceptible genes to PSC. We investigated the expression profiles of these genes in the liver biopsy samples of the patients with PSC, and revealed that the expression of TNFRSF14, which is a one of the risk genes for PSC, was upregulated in the biliary epithelial cell (BEC) of PSC compared to that in normal liver tissue and primary biliary cholangitis (PBC) liver tissue. TNFRSF14 is a member of the tumor necrosis factor receptor superfamily associated with inflammation and fibrosis. We also clarified that the expression of LIGHT, an active ligand for TNFRSF14, was elevated in the BEC of PSC^１). These molecules are mainly expressed on lymphocytes, and in other inflammatory diseases, many reports have mentioned to the associations between these molecules in the sera and the disease progression.

Aims & Methods

Aims: In this study, we aimed to evaluate the concentrations of these molecules in the sera and bile of PSC.
Methods: The concentrations of soluble TNFRSF14 and LIGHT in the sera and bile were measured by enzyme-linked immunosorbent assay. The samples were collected from the following cases:
• Serum: 73 patients with PSC, 35 patients with PBC and 53 healthy controls.
• Bile: 15 patients with PSC, 12 patients with malignant biliary obstruction (MBO), 19 patients with biliary lithiasis (BL).
The bile samples were obtained during endoscopic retrograde cholangiopancreatography. The median values of the serum (s) and bile (b) concentrations of each group were evaluated by Mann-Whittney U test.

Results

sTNFRSF14 in the PSC group was significantly higher than those in the healthy controls (6.301 v.s. 4,247 pg/mL, P < 0.001) and the PBC group (4,987 pg/mL, P < 0.001).
sLIGHT in the PSC group was 87 pg/mL, which was higher than those in the healthy controls (61 pg/mL, P = 0.012), and was comparable to those in the PBC group (106 pg/mL, P = 0.142).
bTNFRSF14 in the PSC group was 2,005 pg/mL, showing no significant difference compared to those in the MBO (1,794 pg/mL, P = 0.516) and the BL group (1,987 pg/mL, P = 0.504).
bLIGHT in the PSC group was 523 pg/mL, remarkably higher than those in the MBO (82 pg/mL, P < 0.001) and the BL group (268 pg/mL, P = 0.024).

Conclusion

sTNFRSF14 in the PSC group was higher than those in the healthy control and the PBC group, and this result was equivalent to the previous report about the upregulated expression in the liver biopsy samples. While soluble LIGHT was secreted non-specifically in the sera of cholestatic liver disease, the elevated bile concentration of LIGHT can be involved in in the unique biology of PSC. ​Further research is needed to elucidate the involvement of these two molecules in the pathogenesis of PSC.

References

1) Digestive Liver Disease 2024 Feb;56(2):305-311.