Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis.
OBJECTIVE
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).


CONCLUSIONS
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.
Braun
Sandra
S
Department of Internal Medicine II, University of Tuebingen, Otfried-Muller-Str. 10, 72076 Tuebingen, Germany.
Berg
Christoph
C
Buck
Sandra
S
Gregor
Michael
M
Klein
Reinhild
R
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D020134:Catalytic Domain / Q000276:immunology*; D051047:Dihydrolipoyllysine-Residue Acetyltransferase / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D008099:Liver / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008930:Mitochondria, Liver / Q000276:immunology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D000939:Epitopes; D016056:Immunodominant Epitopes; D010455:Peptides; D051047:Dihydrolipoyllysine-Residue Acetyltransferase