Conformational anti-cytochrome P4502E1 (CYP2E1) auto-antibodies contribute to necro-inflammatory injury in chronic hepatitis C

Journal of Viral Hepatitis
Early View (Articles online in advance of print)
Published Online: 3 Aug 2010
© 2010 Blackwell Publishing Ltd

S. Sutti 1 , M. Vidali 1 , C. Mombello 1 , M. Sartori 2 and E. Albano 1

1 Department of Medical Sciences and Interdisciplinary Research Centre for Autoimmune Diseases (IRCAD), University "Amedeo Avogadro" of East Piedmont Novara, Italy ; and 2 Gastroenterology Unit, Ospedale Maggiore della Carità, Novara, Italy

Correspondence to Emanuele Albano, Department of Medical Sciences, University "Amedeo Avogadro" of East Piedmont, Via Solaroli 17, 28100 Novara, Italy. E-mail: albano@med.unipmn.it

Copyright © 2010 Blackwell Publishing Ltd

KEYWORDS
autoimmunity • cytochrome P450 • HCV infection • liver fibrosis

ABSTRACT

Summary. 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.

Received December 2009; accepted for publication June 2010

DIGITAL OBJECT IDENTIFIER (DOI)
10.1111/j.1365-2893.2010.01359.x About DOI
 
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