Chloride/bicarbonate exchange in PBC: A clue for pathogenesis?

Abstract

Primary biliary cirrhosis (PBC), a chronic cholestatic process affecting mainly women, is currently considered to be an autoimmune disease with humoral and cellular immunity directed against mitochondrial antigens or crossreactive epitopes^1,2. However, the molecular changes which originate the autoimmune reaction and the mechanisms responsible for altered immunoregulation in PBC are unknown. Many questions concerning the pathogenesis of this disease remain to be answered. For example, there are patients with virtually identical disease who do not present antimitochondrial antibodies. Also, there are cases in which antimitochondrial antibodies develop after the initiation of pathological alterations in the liver. It is also intriguing that ursodeoxycholic acid (UDCA), a bile acid which induces bicarbonaterich choleresis, affords more therapeutic benefit than classical immunosuppressants despite the autoimmune mechanisms involved in the disease³. Moreover, there is no explanation for the functional changes and abnormal distribution of cell antigens observed in isolated biliary epithelial cells (BEC) from PBC patients.