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J Hepatol. 2006 Dec;45(6):844-50. Epub 2006 Sep 28.

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

Author information

  • 1Gastroenterology Division, Hôpital Sainte-Justine, Montreal, Que., Canada. djilali-saiah.idress@recherche-ste-justine.qc.ca

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.

PMID:
17050030
[PubMed - indexed for MEDLINE]
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