Hepatology Highlights

✍ Scribed by Elwyn Elias

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 59 KB
• Volume: 39
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.20265

✦ Synopsis

The work of Matsumura et al. may prove to be a major development in our understanding of the pathogenesis of primary biliary cirrhosis (PBC). Hitherto, despite being the hallmark of the disease, no plausible role in pathogenesis of PBC has been attributed to the antimitochondrial antibodies (AMA). Following its binding to an in vitro cell line transfected with human polymeric immunoglobulin (Ig) receptor, dimeric IgA with specificity for the PDC-E2 component of AMA induced a significant increase of caspase activation, a pro-apoptotic change. Caspase activation was significantly increased in response to IgA from 7/8 AMA positive PBC patients but not in controls (see figure). Caspase activation was demonstrated when the specificity of IgA was for PDC-E2 but not for BCOADC-E2 or OGDC-E2, other mitochondrial antigens that react with AMA. AMA of IgG subtype did not activate the caspase system. The slow course of caspase activation suggested that it was stress mediated rather than a response to binding of IgA to cell surface death receptors. The data are compatible with the hypothesis that IgA with specificity for PDC-E2, as it transits the biliary epithelial cell, binds newly synthesized PDC-E2 that is en route from endoplasmic reticulum to mitochondria, thus disrupting vital functions and threatening cell survival. The selective concentration of IgA in bile and other mucosal secretions may, equally plausibly, be the source of similar pathology in other secretory epithelia, thus accounting for the characteristic "sicca" dry gland problems found in association with PBC. (See HEPATOLOGY 2004;39:1415-1422.