Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis.
Anti-liver cytosol type 1 (LC1) autoantibody is detected in 30% of sera from patients with type 2 autoimmune hepatitis (AIH), and is the only circulating autoantibody in 10% of cases. Human formiminotransferase cyclodeaminase (FTCD) has been shown to be the specific liver antigen recognized by anti-LC1 autoantibodies. The aim of this study was to identify the dominant epitope on human FTCD and to analyze antigenic-site sequences for clues on the development of AIH. Recombinant proteins and peptides covering the entire cDNA of human FTCD were tested against anti-LC1 autoantibodies. Conformational epitopes were found throughout the protein but linear epitopes were found exclusively in the C-terminal 146 amino acids. Two groups of sera with different reactivities were found: 69%of the sera recognized two specific linear epitopes at positions 428-434 (NTPEEKD) and 440-447 (LQEGLRRA) of human FTCD; others reacted only with a discontinuous epitope between the amino acids at position 395 and 528. FTCD autoantibody production is thus a polyclonal-antigen-driven B cell response. Autoantibodies against conformational or discontinuous epitopes were found in all patients and two-thirds also recognized linear epitopes on human FTCD.
Lapierre
Pascal
P
Service de gastroentérologie et nutrition, Hôpital Sainte-Justine, 3175 Côte Ste-Catherine, Montréal, Québec H3T 1C5, Canada.
Johanet
Catherine
C
Alvarez
Fernando
F
D000642:Ammonia-Lyases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015153:Blotting, Western; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D019693:Hepatitis, Autoimmune / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology; D011233:Precipitin Tests; D051381:Rats
D001323:Autoantibodies; D018076:DNA, Complementary; D000939:Epitopes; D000642:Ammonia-Lyases; C500814:Ftcd protein, rat; C020148:formiminotetrahydrofolate cyclodeaminase