Extensive Homology between the Major Immunodominant Mitochondrial Antigen in Primary Biliary Cirrhosis and Helicobacter pylori Does Not Lead to Immunological Cross-reactivity

homology between the major immunodominant mitochondrial antigen in primary biliary cirrhosis and Helicobacter pylori does not lead to immunological cross-reactivity. Scand J Gastroenterol 2004;39:981– 987. Background: Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic disease characterized by the presence of antibodies directed predominantly against the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2). What provokes tolerance breakdown in PBC remains to be established, though there is evidence to indicate that microbes may induce anti-mitochondrial antibodies (AMA) through a mechanism of molecular mimicry. Methods: Having found that urease beta (UREB)22–36 antigen of Helicobacter pylori (HELPY) shares extensive (87%) similarity with PDC-E2212–226, the major mitochondrial autoepitope, it was hypothesized that this would also lead to cross-reactivity. The UREB/PDC-E2 mimics were thus constructed and tested by ELISA in 112 PBC patients and 114 controls. Results: Reactivity to PDC-E2212–226 was found in 104 patients but to UREB22–36 in only 2. In these two patients, the double reactivity was not cross-reactive. The lack of surface antibody accessibility to UREB22–36, as demonstrated through three-dimensional model prediction analysis, may explain this unexpected finding. There was some speculation on whether HELPY UREB22–36 might act a