DECREASED ANION-EXCHANGER-2 IMMUNOREACTIVITY IN THE LIVER OF PATIENTSWITH PRIMARY BILIARY-CIRRHOSIS

Chloride-bicarbonate anion exchanger 2 (AE2) is expressed in a variety of tissues, including the liver and salivary glands, where it may par ticipate in the generation of hydroionic fluxes into secretions, We ha ve previously reported decreased hepatic levels of AE2 messenger RNA i n patients with primary biliary cirrhosis (PBC), a cholestatic conditi on frequently associated with pluriglandular exocrine failure, Here we investigated the expression of AE2 protein in the liver of PBC patien ts, Using a monoclonal antibody against an AE2 peptide, immunohistoche mistry was performed on liver biopsy specimens from subjects with norm al liver (n = 7), patients with PBC (n = 13), and patients with cirrho sis or cholestasis other than PBC (n = 17 and 11, respectively), Immun ostaining was graded from 0 to 7, according to its intensity and distr ibution. AE2 immunoreactivity was observed in normal Livers, as previo usly reported, and in many pathological Liver biopsy specimens, being mainly restricted to canaliculi and the luminal membrane of terminal a nd interlobular bile ducts, Canalicular and ductular scores were signi ficantly reduced in the PBC group compared with each control group (no rmal liver and cirrhosis or cholestasis other than PBC), whereas no di fferences in immunoreactivity scores were observed among control group s, When four patients with primary sclerosing cholangitis (PSC) were a nalyzed, they also differed from those with PBC, These results suggest that PBC is characterized by diminished expression of AFE2 in the liv er, Reduced levels of this transporter protein might be involved in th e pathogenesis of cholestasis in PBC.