Genetic and epigenetic factors in autoimmune reactions toward cytochrome P4502E1 in alcoholic liver disease

Vidali, Matteo; Stewart, Stephen; Rolla, Roberta; Daly, Ann K.; Chen, Yuanneng; Mottaran, Elisa; Jones, David; Leathart, Julian; Day, Christopher P.; Albano, Emanuele

doi:10.1053/jhep.2003.50049

Cited by 66 publications

(50 citation statements)

References 48 publications

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“…Serum anti-CYP2E1 IgG were assessed by an in house immunoenzymatic assay (ELISA) using as antigen purified recombinant human CYP2E1 (22) The testing of anti-CYP2E1 autoreactivity by western blotting and immunoprecipitation assays was performed using 10 pmol of recombinant human CYP2E1 as previously reported (16). …”

Section: Measurement Of Anti-cyp2e1 Autoantibodiesmentioning

confidence: 99%

Serum Autoantibodies Against Cytochrome P450 2E1 (CYP2E1) Predict Severity of Necroinflammation of Recurrent Hepatitis C

Rigamonti

Vidali²,

Donato

et al. 2009

American Journal of Transplantation

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We previously reported that autoantibodies against cytochrome P4502E1 (CYP2E1) are frequent in patients with chronic hepatitis C. As autoimmune reactions are increasingly detected after orthotopic liver transplantation (OLT), this study investigates prevalence and significance of anti-CYP2E1 autoantibodies in 46 patients with post-OLT recurrent hepatitis C.IgG against recombinant human CYP2E1 above the control threshold was detected in 19 out 46 (41%) sera collected immediately before OLT and in 15 out 46 (33%) sera collected at the time of the 12 months follow-up liver biopsy. Although anti-CYP2E1 reactivity was not modified by OLT, the patients with persistently elevated anti-CYP2E1 IgG (n = 12; 26%) showed significantly higher prevalence of recurrent hepatitis with severe necroinflammation and fibrosis than those persistently negative or positive only either before or after OLT. Moreover, the probability of developing severe necroinflammation was significantly higher in persistently anti-CYP2E1-positive subjects. Multivariate regression and Cox analysis confirmed that the persistence of anti-CYP2E1 IgG, together with a history of acute cellular rejection and donor age >50 years, was an independent risk factor for developing recurrent hepatitis C with severe necroinflammation.We propose that autoimmune reactions involving CYP2E1 might contribute to hepatic damage in a subgroup of transplanted patients with recurrent hepatitis C.

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Section: Measurement Of Anti-cyp2e1 Autoantibodiesmentioning

confidence: 99%

Serum Autoantibodies Against Cytochrome P450 2E1 (CYP2E1) Predict Severity of Necroinflammation of Recurrent Hepatitis C

Rigamonti

Vidali²,

Donato

et al. 2009

American Journal of Transplantation

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“…However, antigenspecific autoantibodies are not unique to AH. In fact, CYP2E1-specific IgG autoantibodies are found in patients with alcoholic liver disease (46) and toxic liver injury from commercial refrigerant hydroclorofluorocarbons (12). Moreover, previous studies have suggested that IDDIH caused by antiseizure medications, antidepressants, antibiotics or nonsteroidal anti-inflammatory agents results from immune-mediated hepatocellular injury involving drug hapten-altered cytochrome P450 enzymes (1,6).…”

mentioning

confidence: 99%

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

Njoku

Mellerson

Talor

et al. 2006

Clin Vaccine Immunol

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Idiosyncratic drug-induced hepatitis (IDDIH) is the third most common cause for acute liver failure in the United States. Previous studies have attempted to identify susceptible patients or early stages of disease with various degrees of success. To determine if total serum immunoglobulin subclasses, CYP2E1-specific subclass autoantibodies, complement components, or immune complexes could distinguish persons with IDDIH from others exposed to drugs, we studied persons exposed to halogenated volatile anesthetics, which have been associated with IDDIH and CYP2E1 autoantibodies. We found that patients with anesthetic-induced IDDIH had significantly elevated levels of CYP2E1-specific immunoglobulin G4 (IgG4) autoantibodies, while anesthetic-exposed healthy persons had significantly elevated levels of CYP2E1-specific IgG1 autoantibodies. Anesthetic IDDIH patients had significantly lower levels of C4a, C3a, and C5a compared to anesthetic-exposed healthy persons. C1q-and C3d-containing immune complexes were significantly elevated in anesthetic-exposed persons. In conclusion, our data suggest that anesthetic-exposed persons develop CYP2E1-specific IgG1 autoantibodies which may form detectable circulating immune complexes subsequently cleared by classical pathway activation of the complement system. Persons susceptible to anesthetic-induced IDDIH develop CYP2E1-specific IgG4 autoantibodies which form small, nonprecipitating immune complexes that escape clearance because of their size or by direct inhibition of complement activation.

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“…It is reported that alcoholic liver diseases are associated with autoimmunity. 42,43 Thus, it is likely that patients with alcoholic cirrhosis may have autoantibodies reac- …”

Section: Discussionmentioning

confidence: 99%

Are preformed antibodies to biliary epithelial cells of clinical importance in liver transplantation?

Ericzon

Nowak

et al. 2003

Liver Transplantation

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During acute liver allograft rejection, most of the tissue damage to bile duct epithelium is thought to occur as a consequence of direct immunologic injury by T-cell-mediated immune effector mechanisms. However, the role of antibodies to biliary epithelial cells (BECs) in liver transplant rejection is not known. We therefore investigated cross-match sera obtained immediately before liver transplantation from 95 patients for the presence of BECreactive antibodies to determine their association with acute rejection. BECs were isolated from one normal healthy liver. Antibody binding was detected by using flow cytometric analysis. Donor lymphocyte-specific cross-matches using complement-dependent cytotoxicity (CDC) and flow cytometric assays also were performed. The 2-year patient survival rate in this study was 86.3%.

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Genetic and epigenetic factors in autoimmune reactions toward cytochrome P4502E1 in alcoholic liver disease

Cited by 66 publications

References 48 publications

Serum Autoantibodies Against Cytochrome P450 2E1 (CYP2E1) Predict Severity of Necroinflammation of Recurrent Hepatitis C

Serum Autoantibodies Against Cytochrome P450 2E1 (CYP2E1) Predict Severity of Necroinflammation of Recurrent Hepatitis C

Role of CYP2E1 Immunoglobulin G4 Subclass Antibodies and Complement in Pathogenesis of Idiosyncratic Drug-Induced Hepatitis

Are preformed antibodies to biliary epithelial cells of clinical importance in liver transplantation?

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