ABNORMAL EXPRESSION OF ANION-EXCHANGER GENES IN PRIMARY BILIARY-CIRRHOSIS

Background: Chloride-bicarbonate anion exchangers (AE) are thought to be essential to the generation of ion fluxes into biliary, salivary, pancreatic, and other secretions. In primary biliary cirrhosis (PBC), chronic cholestasis is frequently associated with pluriglandular exocrine failure. The present study examined the expression of AE genes in PBC at the messenger RNA (mRNA) level. Methods: Two AE messages, i.e., AE1 and AE2 mRNAs, were analyzed by a polymerase chain reaction-based procedure in liver specimens and peripheral mononuclear cells of patients with PBC and control subjects (with normal livers or with miscellaneous liver diseases). Results: AE1 mRNA was detected in only a few liver biopsy specimens of patients with PBC and control subjects, whereas AE2 mRNA was found in all liver specimens tested. In lymphoid cells, however, both transcripts were consistently detected. AE2 mRNA levels in liver as well as in lymphoid cells were significantly lower in PBC patients than in controls. In contrast to AE2 mRNA, AE1 mRNA levels were increased in lymphoid cells from patients with PBC. Interestingly, the levels of liver AE2 mRNA in a few PBC patients treated with ursodeoxycholic acid were within the range of the controls. Conclusions: The expression of AE genes is altered in patients with PBC. It is suggested that this disturbance may have a role in the cholestasis, exocrine failure, and immunodysfunction of PBC. © 1992.