title: Frequency and significance of antibodies to P450IID6 protein in Japanese patients with chronic hepatitis C.
abstract: OBJECTIVE
  The aims of the current study were to assess the frequency and the significance of antibodies to cytochrome P450IID6 protein (anti-P450IID6) in various diseases among Japanese patients.
  
  
  METHODS
  Sera from 541 patients were tested by indirect immunofluorescence, and the specificity of anti-P450IID6 was ascertained by either enzyme immunoassay (ELISA) or Western blot using recombinant antigen or rat liver microsomes.
  
  
  RESULTS
  Anti-P450IID6 was found in only 6 of 235 patients (2.6%) with chronic active hepatitis (CAH) positive for hepatitis C virus (HCV) antibody and quantitative HCV-RNA with genotypes II and IV. The predominant epitopes on immunoblots were 66 and 50KD, a 10KD band being the newly underfined microsomal antigen. Even in the patients negative for autoantibodies to nuclear antigens (ANA) by routine indirect immunofluorescence test, various ANA were detected by the newly developed recombinant ELISA. These patients were younger, with lower gamma-globulin and IgG levels than patients with autoimmune hepatitis. Three of five patients with anti-P450IID6 responded well to interferon therapy and one received prednisone when interferon was ineffective. Interestingly, only this patient was diagnosed as definite autoimmune hepatitis according to the criteria proposed by the International Autoimmune Hepatitis Group (IAHG). The other five patients who did not satisfy the IAHG criteria might be considered as CAH-C with autoimmune features. No autoimmune hepatitis patients positive for anti-P450IID6 were identified in the current study, indicating that the variant is very rare in Japan.
  
  
  CONCLUSIONS
  Anti-P450IID6 in CAH-C patients in Japan is not as rare as expected. Anti-P450IID6 among Japanese patients has uncertain significance and precludes further characterization of CAH-C with autoimmune features, which might require interferon therapy.
authors.affiliation: Third Department of Internal Medicine, Kagawa Medical University, Japan. sannai@kms.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Nishioka
authors.forename: S A
authors.initials: SA
authors.lastname: Morshed
authors.forename: K
authors.initials: K
authors.lastname: Kono
authors.forename: T
authors.initials: T
authors.lastname: Himoto
authors.forename: S
authors.initials: S
authors.lastname: Parveen
authors.forename: K
authors.initials: K
authors.lastname: Arima
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies / Q000032:analysis*; D001323:Autoantibodies / Q000032:analysis; D002908:Chronic Disease; D019389:Cytochrome P-450 CYP2D6 / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006526:Hepatitis C / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D051381:Rats; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D006680:HLA Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C060729:anti-liver kidney microsome antibody; D019389:Cytochrome P-450 CYP2D6