Conformational anti-cytochrome P4502E1 (CYP2E1) auto-antibodies contribute to necro-inflammatory injury in chronic hepatitis C.
Circulating auto-antibodies against cytochrome P4502E1 (CYP2E1) have been observed in a significant fraction of patients with chronic hepatitis C (CHC). This study investigated the clinical significance of these auto-antibodies in relation to their antigen specificity. The presence of anti-CYP2E1 IgG was investigated in 137 consecutive patients with biopsy-proven CHC. Anti-CYP2E1 IgG above control threshold levels was detected in 52 (38%) subjects. By combined immunoprecipitation and western blotting, we observed that among anti-CYP2E1 IgG-positive sera, 23 (44%) were unreactive towards denaturated CYP2E1, indicating a prevalent recognition of conformational CYP2E1 antigens. Conformational anti-CYP2E1 auto-antibodies were unrelated to circulating gamma-globulins, alcohol intake or infection by specific HCV genotypes. The presence of anti-CYP2E1 auto-antibodies was associated with an 11-fold (OR 10.9 95%CI 1.4-86.6 P = 0.008) increased prevalence of necro-inflammatory grading ≥ 4 (Ishack's criteria) and 4-fold (OR 4.0; 95%CI 1.3-11-7: P = 0.014) increased prevalence of fibrosis staging ≥ 2, respectively. Multivariate analysis confirmed conformational anti-CYP2E1 IgG (P = 0.005) and age (P = 0.033) as independent predictors of necro-inflammatory grading ≥ 4. The development of anti-CYP2E1 auto-antibodies targeting conformational CYP2E1 epitopes is associated with more severe liver damage in CHC.
Sutti
S
S
Department of Medical Sciences and Interdisciplinary Research Centre for Autoimmune Diseases (IRCAD), University Amedeo Avogadro of East Piedmont, Novara, Italy.
Vidali
M
M
Mombello
C
C
Sartori
M
M
Albano
E
E
D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western / Q000379:methods; D019392:Cytochrome P-450 CYP2E1 / Q000276:immunology*; D005260:Female; D006508:Hepatitis Antibodies / Q000097:blood / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D047468:Immunoprecipitation / Q000379:methods; D008099:Liver / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
D001323:Autoantibodies; D006508:Hepatitis Antibodies; D007074:Immunoglobulin G; D019392:Cytochrome P-450 CYP2E1