Immunoreactivity to Various Human Cytochrome P450 Proteins of Sera from Patients with Autoimmune Hepatitis, Chronic Hepatitis B, and Chronic Hepatitis C

Frequency and significance of anti-glutathione S-transferase autoantibody (anti-GST A1-1) in autoimmune hepatitis

“…We also previously reported that phase I enzymes, such as CYP1A2, 2D6, 3A4, and 2E1, may act as the immunotarget of a subset of AIH or hepatic autoimmunity by immunoblot analysis [29]. Thus, we hypothesized that GST A1-1, one of the phase II multidrug metabolizing enzymes may play a role as an immunotarget in autoimmune liver disorders.…”

Relationship between Autoimmunity and Cancer or Metabolic Abnormality in Liver Diseases

“…Antibodies to oxidatively modified autoantigens were also trapped in the sera of patients with NAFLD and chronic hepatitis C (CH-C). Titers of malondialdehyde (MDA)-adducted NAFLD correlation with hepatic fibrosis [73] anti-oxLDL oxLDL HCV correlation with hepatic steatosis [75] anti-SOD SOD AIH false-positivity for anti-HCV [78] anti-cardiolipin cardiolipin HCV correlation with oxidative stress [79] HCV higher prevalence of portal hypertension [86] HCV lack in the symptoms for anti-phospholipid syndrome [79,[81][82][83][84] HCV concurrent oral lichen planus [87] HCV concurrent mixed cryoglobulin [88] NASH N/A [79] AIH Indicator for more advanced liver fibrosis [89] PBC, PSC indicator for more advanced liver fibrosis [90] anti-CYP2E1 CYP2E1 halothene-induced hepatitis specific to IgG4 type of anti-CYP2E1 [101] alcoholic liver cirrhosis N/A [95,96] AIH N/A [97][98][99] HCV indicator for more severe necroinflammation [97,102] anti-HSP HSP65 AIH molecular mimicry between HSP and SOD [105] HSP70 PBC indicator for disease activity [106] HSP70 HCV inverse correlation with diseae-activity [108] human serum albumin (HSA) were elevated in CH-C patients with severe hepatic steatosis [72]. To the contrary, an increase in titers of antibodies to MDA-HSA was independently associated with the progression of liver fibrosis in patients with NAFLD [73].…”

“…In contrast, circulating antibodies to CYP2E1 were originally detected in the sera of patients with halothane-induced hepatitis [94] and alcoholic liver cirrhosis [95,96]. Recently, CYP2E1 was also identified as a target antigen from patients with AIH [97][98][99], while CYP2D6 has been well recognized as the target antigen of antibodies to liver-kidney microsome type 1 (anti-LKM1) [100]. More recently, Njoku and colleagues revealed that the IgG4 type of antibodies to CYP2E1 was specific to the patients with anesthetic-induced hepatitis [101].…”

“…More recently, Njoku and colleagues revealed that the IgG4 type of antibodies to CYP2E1 was specific to the patients with anesthetic-induced hepatitis [101]. On the other hand, approximately 5-40% of patients with CH-C possessed circulating antibodies to CYP2E1 in their sera [97,102]. The molecular mimicry between HCV NS5 and CYP2E1 may initiate the humoral response to CYP2E1 in those patients [103].…”

Antigenic Epitopes on Human P-glycoprotein Recognized by Autoimmune Hepatitis Autoantibody as a Case Study

“…8) CYP2D6 is considered an immunodominant epitope and target of virus/self cross-reactivity in LKM-1 autoantibodypositive liver disease. 9) An autoantibody against CYP2D6 has been reported [10][11][12][13][14][15] and is located on the cellular surface. 16,17) We reported the presence of autoantibodies against various drug-metabolizing enzymes in AIH sera.…”