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Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas
Author(s) -
Herkel Johannes,
Heidrich Birgit,
Nieraad Nicole,
Wies Ingrid,
Rother Michael,
Lohse Ansgar W.
Publication year - 2002
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2002.30699
Subject(s) - epitope , autoantibody , molecular mimicry , antigen , immunodominance , immunology , autoimmunity , biology , autoimmune hepatitis , antibody , pathogenesis , virology , hepatitis
Autoantibodies to soluble liver antigen and liver pancreas (SLA/LP) have been described as specific markers for Autoimmune Hepatitis (AIH), occurring in about 20% of patients with AIH. The high degree of specificity for SLA/LP in autoimmune liver disease suggests a possible role in its pathogenesis. This study aims to map the exact epitope(s) recognized by SLA/LP autoantibodies and to assess the role of molecular mimicry between microbial antigens and self‐epitopes. Using SLA/LP‐reactive sera of 18 individual AIH patients and a pool of 15 patient sera, we found the dominant immune reactivity directed to peptide p395‐414 and a less prominent immune response to 2 other epitopes adjacent to the dominant epitope. Immunodominance of peptide p395‐414 was confirmed by absorption experiments. The SLA/LP autoantibodies of all tested AIH patients were mainly of the IgG1 type, suggesting that SLA/LP autoantibodies may arise by a common and specific underlying immune stimulus. Based on sequence homologies of the SLA/LP antigenic region with viral proteins, it was hypothesized that molecular mimicry may drive autoimmunity to SLA/LP. However, the homologous virus‐derived peptides were not recognized by SLA/LP autoantibodies. Similarly, the only known procaryotic homologue, MJ0610 of Methanococcus jannaschii, was only weakly recognized by SLA/LP‐positive sera. Thus, no evidence could be found for molecular mimicry being the causative mechanism for the development of SLA/LP autoantibodies. In conclusion, the exquisite epitope specificity and IgG subtype are evidence for the maturity of the SLA/LP autoantibody response; a specific autoantigen‐driven process underlying the immunopathogenesis is likely.