REDUCED EXPRESSION OF CELLULAR FOS GENE IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS OF PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS

Abnormal expression of certain cellular oncogenes in peripheral blood mononuclear cells (PBMC) is associated with several autoimmune disorde rs and is thought to reflect a pathologically activated state in vario us lymphocytic subpopulations. Using the Northern blot hybridization t echnique, we studied the expression of cellular (c-)fos, c-myc and N-r as genes in PBMC isolated from patients with primary biliary cirrhosis (PBC) and normal control subjects. The expression of c-fos gene was r educed significantly in patients with PBC, while there was no signific ant difference between the two groups in the expression of c-myc and N -ras genes. Stimulation of PBMC with mitogens in vitro increased c-fos gene expression markedly to a similar extent in both normal subjects and in patients with PBC. Furthermore, the reduced expression of c-fos gene recovered significantly in all the patients examined after treat ment with ursodeoxycholic acid (UDCA). These results suggest that the reduced expression of c-fos gene in PBMC is a reversible functional ma nifestation of PBC and that UDCA therapy for PBC may improve abnormal lymphocyte function.