ABNORMAL EXPRESSION OF PDC-E(2) ON THE APICAL SURFACE OF BILIARY EPITHELIAL-CELLS IN PATIENTS WITH ANTIMITOCHONDRIAL ANTIBODY-NEGATIVE PRIMARY BILIARY-CIRRHOSIS

The presence of antimitochondrial antibodies (AMA) is a major criterio n for the diagnosis of primary biliary cirrhosis (PBC). Although it is not clear that AMA are involved in the pathogenesis of the disease, t he study of these autoantibodies has enabled much information to be ac cumulated about the specificity of this response. The autoantigens hav e been identified as components of a functionally related enzyme famil y, the 2-oxo-acid-dehydrogenase complex. Within this complex, pyruvate dehydrogenase E(2) subunit (PDC-E(2)) has been determined to be the i mmunodominant autoantigen. Using a panel of mouse monoclonal antibodie s and human combinatorial autoantibodies, it has been demonstrated tha t patients with PBC, but not controls, have an abnormal expression of either PDC-E(2) or a cross-reading molecule in the apical region of bi liary epithelium. Others have shown a similar reaction using rabbit se ra directed to PDC-E(2). Our previous studies have concentrated on AMA -positive patients. In this study, the presence of PDC-E(2), class II, immunoglobulin (Ig) A, and B7/BB1 in the bile duct epithelial cells o f AMA-positive as well as AMA-negative patients is addressed. Most pat ients with AMA-negative PBC (seven of nine) react in a fashion similar to AMA-positive patients with intense staining of the apical region o f the bile duct epithelial cells for ''PDC-E(2)'', increased IgA expre ssion, and little major histocompatibility complex (MHC) class II stai ning in the early-stage patients. Interestingly, the two AMA-negative patients that did not express PDC-E(2) on the apical side of their bil iary epithelium had anticentromere antibodies and Sjogren's syndrome. Based on these data, it can be concluded that the disease process for both AMA-positive and AMA-negative patients with PBC has a similar pat hogenic mechanism, which is likely to involve the abnormal expression of PDC-E(2) or a molecular mimic of PDC-E(2), and does not require MHC class II expression.