Brief Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Feb 28, 2010; 16(8): 973-981
Published online Feb 28, 2010. doi: 10.3748/wjg.v16.i8.973
Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis
Sandra Braun, Christoph Berg, Sandra Buck, Michael Gregor, Reinhild Klein
Sandra Braun, Sandra Buck, Reinhild Klein, Department of Internal Medicine II, University of Tuebingen, 72076 Tuebingen, Germany
Christoph Berg, Michael Gregor, Department of Internal Medicine I, University of Tuebingen, 72076 Tuebingen, Germany
Author contributions: Braun S and Buck S performed the research; Berg C and Gregor M provided patients’ serum samples and clinical data; Braun S and Klein R analyzed the data; Klein R designed the research and wrote the paper.
Correspondence to: Reinhild Klein, MD, Associate Professor, Department of Internal Medicine II, University of Tuebingen, Otfried-Muller-Str. 10, 72076 Tuebingen, Germany.
Telephone: +49-7071-2984479 Fax: +49-7071-292760
Received: September 29, 2009
Revised: November 25, 2009
Accepted: December 2, 2009
Published online: February 28, 2010

AIM: To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC).

METHODS: Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore, the inner lipoyl peptide 167-184 was used in an unlipoylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA positive PBC patients, 63 patients with other liver disorders and 22 healthy blood donors served as controls.

RESULTS: Of the 95 PBC-sera, 74% reacted with the peptide 475-499 and 58% with the peptide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylated and lipoylated peptide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera, respectively; using ovalbumin-coupled peptides, the incidence increased up to 57% (unlipoylated form).

CONCLUSION: Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodominant epitopes recognized by AMA in PBC.

Keywords: Anti-M2, Epitope mapping, E2-subunit, Pyruvate dehydrogenase complex, Inner lipoyl domain, Active site, Catalytic domain, Primary biliary cirrhosis