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J Hepatol ; 45(6): 844-50, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17050030

ABSTRACT

BACKGROUND/AIMS: Type 2 autoimmune hepatitis (AIH) is characterized by the presence of anti-liver kidney microsome (anti-LKM-1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. However, the correlation between these autoantibodies and the genetic background has not been studied. METHODS: Frequencies of HLA class II alleles were compared between the 60 Caucasian children with type 2 AIH and 313 control subjects. The anti-LKM1 antibody reactivity directed against antigenic sites of CYP2D6 was analysed by ELISA. RESULTS: HLA-DQB1 *0201 allele was found to be the primary genetic determinant of susceptibility to type 2 AIH by conferring the highest odd-ratio (OR = 6.4). HLA-DRB1 *03 allele was significantly increased (P < 0.0001) among patients with both anti-LKM1 and anti-LC1 autoantibodies as well as in those with only anti-LC1(+) compared to those with anti-LKM1(+) alone. In contrast, HLA-DRB1 *07 allele was significantly associated (P < 0.0001) with anti-LKM1(+) alone compared to groups with both anti-LKM and anti-LC1 or with LC1+ alone. Children with the DRB1 *07 allele develop anti-LKM1 autoantibodies having a more restricted specificity (2 epitopes) than to those having HLA-DRB1 *03 allele (5 epitopes). CONCLUSIONS: The HLA-DR locus is involved in autoantibody expression, while the DQ locus appears to be a critical determinant for the development of type 2 AIH.


Subject(s)
Autoantibodies/immunology , Autoimmunity , Genes, MHC Class II/immunology , Hepatitis, Autoimmune/immunology , Adolescent , Alleles , Autoantigens/immunology , Child , Child, Preschool , Cytochrome P-450 CYP2D6/genetics , Cytochrome P-450 CYP2D6/immunology , Cytochrome P-450 CYP2D6/metabolism , Epitopes , Female , Genes, MHC Class II/genetics , Genetic Predisposition to Disease , Genotype , HLA-DQ Antigens/genetics , HLA-DQ beta-Chains , HLA-DR Antigens/genetics , HLA-DRB1 Chains , Hepatitis, Autoimmune/genetics , Hepatitis, Autoimmune/metabolism , Humans , Infant , Male
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