Projects / Autoimmune mediate diseases / Primary Biliary Cirrhosis

Post translational modified peptides to study autoantibody response in Primary Biliary Cirrhosis


In collaboration with:

University of Milan Clinical Immunology, Humanitas Clinical and Research Center and University of California, Davis

Carlo Selmi

Primary Biliary Cirrhosis (PBC) is a chronic cholestatic liver disease characterized by destruction of bile ducts and the presence in the serum of antimitochondrial antibodies (AMA positive in 90-95% of patients), directed against the E2, which is one of the three component enzymes of the 2-oxo acid dehydrogenase multienzyme complex family chiefly pyruvate dehydrogenase complex (PDC-E2). Environmentally induced co- or post-translational modifications of autoantigens are hypothesized to break immune tolerance leading to self reactivity in PBC. The aim of our research is to develop new diagnostic tools that can be used in earlier stage patients and possibly to monitor disease activity. We synthesized lipoamide and glyco-peptides characterized by a b-hairpin structure with the modification on the tip of the b-turn as peptidomimetic of native antigens involved in PBC. The antibody recognition in PBC sera by ELISA using the modified peptides is compared with the proposed autoepitope of PDC-E2 [PDH(44-63)]. The synthetic antigens are able to detect by ELISA autoantibodies in 30% of AMA negative sera of PBC patients confirming that PTM-peptides are useful diagnostic/prognostic tools.








The structure of native antigens involved in PBC.