Detection of auto-antibodies against cytochrome P4502E1 (CYP2E1) in chronic hepatitis C

• Published in: Journal of hepatology 2007-04, Vol.46 (4), p.605-612
• Main Authors: Vidali, Matteo, Occhino, Giuseppa, Ivaldi, Alessandra, Serino, Roberto, Moia, Stefania, Alchera, Elisa, Carini, Rita, Rigamonti, Cristina, Sartori, Massimo, Albano, Emanuele
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alcohol Drinking; Animals; Auto-immunity; Autoantibodies - blood; Biological and medical sciences; Cell Membrane - metabolism; Cytochrome P-450 CYP2E1 - immunology; Cytochrome P-450 CYP2E1 - metabolism; Cytochrome P450; Female; Gastroenterology and Hepatology; Hepatitis C; Hepatitis C, Chronic - immunology; Hepatitis C, Chronic - metabolism; Hepatitis C, Chronic - physiopathology; Hepatocytes - metabolism; Human viral diseases; Humans; Immunoglobulin G - immunology; Infectious diseases; Male; Medical sciences; Microscopy, Confocal; Middle Aged; Rats; Rats, Sprague-Dawley; Severity of Illness Index; Tissue Distribution; Viral diseases; Viral hepatitis
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2006.11.009

Background/Aims Chronic hepatitis C (CHC) is often associated with auto-immune reactions. In the light of the role of alcohol in promoting CHC progression, we have investigated the possible presence of auto-reactivity against the ethanol-inducible cytochrome P4502E1 (CYP2E1) in CHC patients with and without alcohol consumption. Methods The IgG reactivity against recombinant human CYP2E1 was evaluated by solid-phase immunoassays in 102 CHC patients with different alcohol consumption and 59 HCV-free controls. Results Auto-antibodies against CYP2E1 were significantly ( p < 0.0001) increased in CHC patients as compared to controls. Anti-CYP2E1 IgG above the 97th percentile in the controls were evident in 41 (40%) CHC patients. Competition experiments revealed that CYP2E1 recognition was not due to the cross-reactivity with CYP2D6. The detection of anti-CYP2E1 IgG was unrelated to alcohol consumption and no difference in gender, age, aminotransferase levels and virus genotype was evident among the patients with or without anti-CYP2E1 auto-antibodies. However, anti-CYP2E1 auto-reactivity was significantly ( p = 0.025) associated with the severity of periportal/periseptal interface hepatitis. Moreover, confocal microscopy demonstrated that anti-CYP2E1 IgG associated with CHC recognized CYP2E1 exposed on the outer side of hepatocyte plasma membranes. Conclusions HCV infection favours the breaking of self-tolerance against CYP2E1 that might contribute to hepatocyte injury.