Cytochrome P450 2A6: a new hepatic autoantigen in patients with chronic hepatitis C virus infection

Breaking self-tolerance toward cytochrome P4502E1 (CYP2E1) in chronic hepatitis C: Possible role for molecular mimicry

“…Although alcohol abuse has been shown to stimulate the breaking of self-tolerance toward CYP2E1 [11], in our hands alcohol intake by CHC patients does not influence anti-CYP2E1 IgG prevalence [18]. Furthermore, the fact that anti-CYP selfreactivity in CHC is highly specific to individual CYPs [15][16][17] and no cross-reactivity occurs between anti-CYP2E1 antibodies and CYP2D6 [18], this rules out the possibility that CYP release from damaged hepatocytes might trigger the breaking of selftolerance. Current research on the mechanisms by which HCV infection promotes the onset of autoimmune reactions have focused on the peculiar ability of HCV to stimulate B-lymphocyte activation as well as on molecular mimicry [3][4][5][6]15].…”

“…Furthermore, antibodies against CYP2A6, CYP3A4, and CYP2E1 have been also observed in CHC patients [16,17]. In this latter respect, we have recently reported that about 40% of CHC patients have increased titers of IgG recognizing human CYP2E1 in immuno-enzymatic assays [18].…”

Localization of CYP4B1 in the rat nasal cavity and analysis of CYPs as secreted proteins

“…Sera positive for both hepatitis C and the anti-liver-kidney microsomal antigen-1 (LKM1) recognize a specific conformational epitope on CYP2D6 between amino acids 254 and 288, the region that contains the major linear epitope in type 2 autoimmune hepatitis patients [12]. Immunoreactivity toward other CYPs (e.g., CYP1A2, CYP2C9, CYP2A6), as well as UGT1A6, has been observed in other patients diagnosed with autoimmune hepatitis, as well as viral hepatitis or autoimmune polyglandular syndrome [13][14][15]. Therefore, it appears that CYPs can be presented as antigens on the plasma membrane of hepatocytes under conditions that are not yet clearly understood and provoke autoimmune liver damage.…”

Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group

“…Anti LM antibodies stain only the liver cytoplasm and not the kidney or other organs, react with liver specific cytochrome P4501A2 [33,34] and occur in dihydralazine induced hepatitis [33] and in hepatitis associated with the autoimmune polyendocrine syndrome type 1 (APS-1) [35]. An anti-LKM-1 like pattern of immunofluorescence is given by autoantibodies to P4502A6, as judged by recombinant cytochrome P4502A6 based immunoassays [36,37]; these antibodies occur in APS-1 and occasionally in hepatitis C, but in contrast to anti-LM they are not specifically associated with liver disease in APS-1.The term anti-LKM-2 was originally applied to LKM-1-like microsomal antibodies produced during hepatitis induced by tienilic acid [38] (no longer marketed) and are directed against cytochrome P4502C9. Anti LKM-3 also gives an immunofluorescent pattern resembling that of anti-LKM-1, but these antibodies occur in hepatitis D (delta), and rarely in autoimmune hepatitis type 2 [39]; they react with members of the family 1 UDP glucuronosyltransferases (UGT) and target an epitope common to all members of this family [40][41][42].…”