Epitopes described in "Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas."

Article Authors:Johannes Herkel; Birgit Heidrich; Nicole Nieraad; Ingrid Wies; Michael Rother; Ansgar W Lohse
Article Title:Fine specificity of autoantibodies to soluble liver antigen and liver/pancreas.
Reference Detail
Reference ID:1017212
Abstract: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.
Affiliations:I. Department of Medicine, Johannes Gutenberg-Universit├Ąt, Mainz, Germany.
Reference Type:Literature
PubMed ID:11826415
Journal Volume:35
Article Pages:403-8
Journal ISSN:0270-9139
Article Chemical List:Antigens, Bacterial;Antigens, Viral;Autoantibodies;Autoantigens;Epitopes;Immunoglobulin G;Immunoglobulin Isotypes;Peptide Fragments;liver antigen LA-1
Article MeSH List:Antibody Specificity; Antigens, Bacterial(genetics; immunology); Antigens, Viral(immunology); Autoantibodies(immunology); Autoantigens(chemistry; immunology); Cross Reactions; Epitopes; Hepatitis, Autoimmune(immunology); Humans; Immunoglobulin G(immunology); Immunoglobulin Isotypes(immunology); Molecular Mimicry; Peptide Fragments(immunology)
Curation Last Updated:2014-10-03 21:50:06