Abstract:
:Characterization of liver-specific autoantigens has given a fresh impetus to research in the pathogenesis of autoimmune liver diseases, viral-triggered and drug-induced autoimmunity affecting the liver. Intriguing is the fact that most of the liver-specific autoantigens are enzymes of key importance for cell's homeostasis. Detection of autoantibodies against the respective antigens is carried out for diagnostic and research purposes using indirect immunofluorescence, immunoblotting, enzyme-linked immunosorbent assays, radioimmunoassay, immunoprecipitation or assays determining inhibition of enzyme activity. In patients with autoimmune hepatitis, a liver disorder of unknown etiology and pathogenesis, disease-specific autoantibodies are frequently directed against drug metabolizing enzymes of phase 1, namely cytochrome P450 2D6 (CYP2D6). The same and other members of these families of enzymes (CYPs) have also been described as targets of liver-specific autoimmunity in chronic hepatitis C virus (HCV)-infected patients, patients with autoimmune hepatitis as part of the autoimmune polyglandular syndrome type-1 (APS-1) and drug-induced autoimmunity. How these enzymes become 'self targets' is not yet established. An antigen release following hepatocyte injury could provide the stimulus for an immune response towards epitopes on these enzymes but the highly-specific, antigen-restricted initiation of the observed autoimmune response is against such an explanation. Accordingly, in this review we will focus on the pathogenic role -if any- of autoimmune responses against liver-related CYPs in autoimmune hepatitis, HCV infection, APS-1 and drug-induced autoimmunity. Learning more about the specificity of antibody responses against these enzymes may help us better understand the mechanisms underlying liver autoimmunity and may facilitate the development of therapeutic and preventive interventions.
journal_name
Curr Med Chemjournal_title
Current medicinal chemistryauthors
Bogdanos DP,Dalekos GNdoi
10.2174/092986708785747508subject
Has Abstractpub_date
2008-01-01 00:00:00pages
2285-92issue
22eissn
0929-8673issn
1875-533Xjournal_volume
15pub_type
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更新日期:2014-01-01 00:00:00
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