Significance of serum Fas-ligand levels in patients with primary biliary cirrhosis and its relationship to histological Fas-ligand expression

Abstract

The mechanism of bile duct destruction observed in primary biliary cirrhosis (PBC) is still not clear. Recent study regarding cell death suggests the contribution of perforinor Fas-related apoptosis in the pathogenesis of immune-mediated cholangiopathy. The measurement of Fas-ligand (Fas-L) has been available recently and serum Fas-L level is reportedly related to the various inflammatory processes. However, its importance in immunemediated cholangiopathy is not known. Also, the usefulness of measuring Fas-L for evaluation of the clinical stage or activity is not known. Thus the Aims of this study are; (1) to measure the Fas-L in the serum from patients with PBC and compare their Fas-L levels to clinical parameters, (2) to compare Fas-L levels in PBC patients with those in other autoimmune liver disease patients (autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC)), and (3) to examine the relationship between serum Fas-L levels and histological Fas-L expression of the liver-infiltrating lymphocytes. [Methods] Histologically diagnosed 43 PBC cases, 5 AIH cases, and 2 PSC cases were enrolled in this study. The clinical parameters analyzed included serum ALT, ALP, IgG, IgM levels and histological staging of PBC by Scheuer. Serum Fas-L level was measured by ELISA. The Fas-L expression in liver specimens from PBC patients was evaluated by indirect immunohistochemistry using anti-Fas-L antibody. The density of Fas-L positive cells in the portal tract were calculated using NIH image, and evaluated in accordance with the degree of cholangitis and fibrosis in routine HE PBC 0.55 1.01, AIH 0.84 + 0.62, PSC 2.20--. 2.54, and the difference was not significant. (2) There was no statistical corelation between serum Fas-L levels and other clinical parameters (serum ALT, ALP, IgG, IgM levels). (3) In PBC, scattered Fas-L-positive cells were observed. The number of Fas-L positive cells per portal tract (mean_+ SD) was 2.79 +-1.21 (range 1.29 to 5.14). However, there was no statistical corelation of those positivities of histological Fas-L expression with serum Fas-L levels or degree of fiborsis/cholangitis. [Conclusions] Measurement of serum Fas-L levels were possible in human cholangiopathies including PBC. However, its relationship to other clinical factors and histological Fas-L expression was not proved. This research was funded by the grant from the Ministry of Education of Japan #07670555 and #09770339.