A comparative study of antibody expressions in primary biliary cirrhosis and autoimmune cholangitis using phage display

Ikuno, Nobuhiro, Scealy, Marita, Davies, Janet M., Whittingham, Senga F., Omagari, Katsuhisa, MacKay, Ian R. and Rowley, Merrill J. (2001) A comparative study of antibody expressions in primary biliary cirrhosis and autoimmune cholangitis using phage display. Hepatology, 34 3: 478-486.


Author Ikuno, Nobuhiro
Scealy, Marita
Davies, Janet M.
Whittingham, Senga F.
Omagari, Katsuhisa
MacKay, Ian R.
Rowley, Merrill J.
Title A comparative study of antibody expressions in primary biliary cirrhosis and autoimmune cholangitis using phage display
Journal name Hepatology
Publication date 2001-09
Sub-type Article
DOI 10.1053/jhep.2001.27013
Volume number 34
Issue number 3
ISSN 0270-9139; 1527-3350
Start page 478
End page 486
Total pages 9
Place of publication Hoboken, NJ, U.S.A.
Publisher John Wiley & Sons
Language eng
Subject C1
1103 Clinical Sciences
Formatted abstract Primary biliary cirrhosis (PBC) and autoimmune cholangitis (AIC) are serologic expressions of an autoimmune liver disease affecting biliary ductular cells. Previously we screened a phage-displayed random peptide library with polyclonal IgG from 2 Australian patients with PBC and derived peptides that identified a single conformational (discontinuous) epitope in the inner lipoyl domain of the E2 subunit of the pyruvate dehydrogenase complex (PDC-E2), the characteristic autoantigen in PBC. Here we have used phage display to investigate the reactivity of PBC sera from 2 ethnically and geographically distinct populations, Japanese and Australian, and the 2 serologic expressions, PBC and AIC. Random 7-mer and 12-mer peptide libraries were biopanned with IgG from 3 Japanese patients with PBC and 3 with AIC who did not have anti–PDC-E2. The phage clones (phagotopes) obtained were tested by capture enzyme-linked immunosorbent assay (ELISA) for reactivity with affinity-purified anti–PDC-E2, and compared with those obtained from Australian patients with PBC. Peptide sequences of the derived phagotopes and sequences derived by biopanning with irrelevant antisera were aligned to develop a guide tree based on physicochemical similarity. Both Australian and Japanese PBC-derived phagotopes were distributed in branches of the guide tree that contained the peptide sequences MH and FV previously identified as part of an immunodominant conformational epitope of PDC-E2, indicating that epitope selection was not influenced by the racial origin of the PBC sera. Biopanning with either PBC or AIC-derived IgG yielded phagotopes that reacted with anti–PDC-E2 by capture ELISA, further establishing that there is a similar autoimmune targeting in PBC and AIC.
© John Wiley and Sons 2001.
Keyword Random peptide libraries
Systemic lupus-erythematosus
Human pdc-e2-163-176 peptide
Mitochondrial autoantigens
Epitopes
Mimotopes
Q-Index Code C1

Document type: Journal Article
Sub-type: Article
Collection: School of Medicine Publications
 
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