HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis.
OBJECTIVE
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.
Djilali-Saiah
Idriss
I
Gastroenterology Division, Hôpital Sainte-Justine, Montreal, Que., Canada. djilali-saiah.idress@recherche-ste-justine.qc.ca
Fakhfakh
Amin
A
Louafi
Hamida
H
Caillat-Zucman
Sophie
S
Debray
Dominique
D
Alvarez
Fernando
F
D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000939:Epitopes; D005260:Female; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C060729:anti-liver kidney microsome antibody; C077285:liver cytosol antigen type 1, human; D019389:Cytochrome P-450 CYP2D6