HLA Class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis

• Published in: Journal of hepatology Vol. 45; no. 6; pp. 844 - 850
• Main Authors: Djilali-Saiah, Idriss, Fakhfakh, Amin, Louafi, Hamida, Caillat-Zucman, Sophie, Debray, Dominique, Alvarez, Fernando
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.12.2006; Elsevier
• Subjects: Adolescent; Alleles; Antigens/Peptides/Epitopes; Autoantibodies; Autoantibodies - immunology; Autoantigens - immunology; Autoimmunity; Biological and medical sciences; Child; Child, Preschool; Cytochrome P-450 CYP2D6 - genetics; Cytochrome P-450 CYP2D6 - immunology; Cytochrome P-450 CYP2D6 - metabolism; Epitopes; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, MHC Class II - genetics; Genes, MHC Class II - immunology; Genetic Predisposition to Disease; Genotype; Hepatitis, Autoimmune - genetics; Hepatitis, Autoimmune - immunology; Hepatitis, Autoimmune - metabolism; HLA-DQ Antigens - genetics; HLA-DQ beta-Chains; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Human; Humans; Infant; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; MHC; Other diseases. Semiology; AIH; LKM-1; Human; Autoimmunity; Antigens/Peptides/Epitopes; SSP; Autoantibodies; ANA; SMA; MHC; LC1; Immunopathology; Antigenic determinant; Peptides; Major histocompatibility system; Class II histocompatibility antigen; Autoantibody; Hepatic disease; Autoimmune disease; Hepatitis; Digestive diseases; Humoral immunity
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2006.07.034

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. 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. 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). 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.