Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver cytosol antibody type 1

Authors

  • Luigi Muratori M.D., Ph.D.,

    Corresponding author
    1. Departments of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
    • Department of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum, University of Bologna, Policlinico S. Orsola, via Massarenti, 9, 40138 Bologna, Italy. fax: (39) 051-340877
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  • Elizabeth Sztul,

    1. Department of Clinical and Experimental Medicine, Section of Microbiology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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  • Paolo Muratori,

    1. Departments of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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  • Ya-sheng Gao,

    1. Department of Clinical and Experimental Medicine, Section of Microbiology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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  • Alessandro Ripalti,

    1. Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL.
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  • Cristina Ponti,

    1. Departments of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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  • Marco Lenzi,

    1. Departments of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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  • Maria Paola Landini,

    1. Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL.
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  • Francesco B. Bianchi

    1. Departments of Internal Medicine, Cardioangiology, Hepatology, Alma Mater Studiorum, University of Bologna, Bologna, Italy
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Abstract

Liver cytosol antibody type 1 (LC1) is regarded as a serologic marker of type 2 autoimmune hepatitis, in addition to liver kidney microsomal antibody type 1. Among 38 patients with type 2 autoimmune hepatitis, 23 were positive for LC1 antibodies. The antigen recognized by LC1 has been identified as a liver-specific 58-kd metabolic enzyme named formiminotransferase cyclodeaminase (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, 10 with primary biliary cirrhosis, 10 with chronic hepatitis C, and 10 healthy 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 distinct globular FT and CD domains connected by a short linker. To identify epitopes that trigger the LC1 autoimmune response, we tested LC1 antibodies against FTCD constructs encoding the N-terminal FT domain (amino acids 1-339), 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 domain, 7 (35%) recognized only the FT domain, and 5 (25%) did not recognize either construct. No sera reacted with only the CD domain. These data indicate that multiple regions of FTCD trigger the LC1 autoimmune response, and that LC1 reactivity is mainly directed to conformation-sensitive epitopes located in the FT region of FTCD. (HEPATOLOGY 2001;34:494-501.)

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