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

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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Djilali-Saiah I,Fakhfakh A,Louafi H,Caillat-Zucman S,Debray D,Alvarez F

doi

10.1016/j.jhep.2006.07.034

subject

Has Abstract

pub_date

2006-12-01 00:00:00

pages

844-50

issue

6

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(06)00452-1

journal_volume

45

pub_type

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