Detection of auto-antibodies against cytochrome P4502E1 (CYP2E1) in chronic hepatitis C.
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.
Vidali
Matteo
M
Department of Medical Sciences, University Amedeo Avogadro of East Piedmont and Interdepartmental Research Centre for Autoimmune Diseases (IRCAD), Novara, Italy.
Occhino
Giuseppa
G
Ivaldi
Alessandra
A
Serino
Roberto
R
Moia
Stefania
S
Alchera
Elisa
E
Carini
Rita
R
Rigamonti
Cristina
C
Sartori
Massimo
M
Albano
Emanuele
E
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
D001323:Autoantibodies; D007074:Immunoglobulin G; D019392:Cytochrome P-450 CYP2E1