Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmuneliver cytosol antibody type 1

Citation
L. Muratori et al., Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmuneliver cytosol antibody type 1, HEPATOLOGY, 34(3), 2001, pp. 494-501
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
HEPATOLOGY
ISSN journal
0270-9139 → ACNP
Volume
34
Issue
3
Year of publication
2001
Pages
494 - 501
Database
ISI
SICI code
0270-9139(200109)34:3<494:DEOFCI>2.0.ZU;2-T
Abstract
Liver cytosol antibody type 1 (LC1) is regarded as a serologic marker of ty pe 2 autoimmune hepatitis, in addition to liver kidney microsomal antibody type 1. Among 38 patients with type 2 autoimmune hepatitis, 23 were positiv e for LC 1 antibodies. The antigen recognized by LC 1 has been identified a s a liver-specific 58-kd metabolic enzyme named formiminotransferase cyclod eaminase (FTCD). All 23 LC1-positive sera immunoprecipitated rat FTCD, and 22 gave an identity reaction with rat FTCD by immunodiffusion. No reaction was observed with sera from 10 patients with type 1 autoimmune hepatitis, 1 0 with primary biliary cirrhosis, 10 with chronic hepatitis C, and 10 healt hy controls. By Western immunoblotting all 23 LC1-positive sera and all the controls tested negative, suggesting that all the antigenic epitopes were destroyed by denaturation. FTCD is a bifunctional protein composed of disti nct globular FT and CD domains connected by a short linker. To identify epi topes that trigger the LC I. autoimmune response, we tested LC I antibodies against FTCD constructs encoding the N-terminal FT domain (amino acids 1-3 39), or the C-terminal CD domain (amino acids 332-541). Of 20 sera positive against full-length FTCD, 8 (40%) recognized the FT domain and the CD doma in, 7 (35%) recognized only the FT domain, and 5 (25%) did not recognize ei ther construct. No sera reacted with only the CD domain. These data indicat e that multiple regions of FTCD trigger the LC1 autoimmune response, and th at LC 1 reactivity is mainly directed to conformation-sensitive epitopes lo cated in the FT region of FTCD.