title: Detection of auto-antibodies against cytochrome P4502E1 (CYP2E1) in chronic hepatitis C.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medical Sciences, University Amedeo Avogadro of East Piedmont and Interdepartmental Research Centre for Autoimmune Diseases (IRCAD), Novara, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Vidali
authors.forename: Giuseppa
authors.initials: G
authors.lastname: Occhino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ivaldi
authors.forename: Roberto
authors.initials: R
authors.lastname: Serino
authors.forename: Stefania
authors.initials: S
authors.lastname: Moia
authors.forename: Elisa
authors.initials: E
authors.lastname: Alchera
authors.forename: Rita
authors.initials: R
authors.lastname: Carini
authors.forename: Cristina
authors.initials: C
authors.lastname: Rigamonti
authors.forename: Massimo
authors.initials: M
authors.lastname: Sartori
authors.forename: Emanuele
authors.initials: E
authors.lastname: Albano
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D000818:Animals; D001323:Autoantibodies / Q000097:blood*; D002462:Cell Membrane / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014018:Tissue Distribution
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D019392:Cytochrome P-450 CYP2E1