Role of Lipoylationof the Immunodominant Epitopeof Pyruvate Dehydrogenase Complex: Toward a Peptide-Based Diagnostic Assay for Primary BiliaryCirrhosis.

Primary biliary cirrhosis is an immune-mediatedchronic liver diseasewhose diagnosis relies on the detection of serum antimitochondrialantibodies directed against a complex set of proteins, among whichpyruvate dehydrogenase complex is considered the main autoantigen.We studied the immunological role of the lipoyl domain of this proteinusing synthetic lipoylated peptides, showing that the lipoyl chainchirality does not affect autoantibody recognition and, most importantly,confirming that both lipoylated and unlipoylated peptides are ableto recognize specific autoantibodies in patients sera. In fact, 74%of patients sera recognize at least one of the tested peptides butvery few positive sera recognized exclusively the lipoylated peptide,suggesting that the lipoamide moiety plays a marginal role withinthe autoreactive epitope. These results are supported by a conformationalanalysis showing that the lipoyl moiety of pyruvate dehydrogenasecomplex appears to be involved in hydrophobic interactions, whichmay limit its exposition and thus its contribution to the complexantigenic epitope. A preliminary analysis of the specificity of thetwo most active peptides indicates that they could be part of a panelof synthetic antigens collectively able to mimic in a simple immunoenzymaticassay the complex positivity pattern detected in immunofluorescence. [ABSTRACT FROM AUTHOR]