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Characterization of the B cell response of patients with anti‐liver cytosol autoantibodies in type 2 autoimmune hepatitis
Author(s) -
Lapierre Pascal,
Johanet Catherine,
Alvarez Fernando
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200323857
Subject(s) - epitope , autoantibody , polyclonal antibodies , biology , antigen , epitope mapping , autoimmune hepatitis , microbiology and biotechnology , immunology , antibody , virology , hepatitis
Abstract 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.