Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70-74 of the HLA-DRB1 molecule.
OBJECTIVE
The risk of developing autoimmune hepatitis (AIH) has been suggested to be associated with the presence of HLA-DRB1 alleles encoding the 'shared epitope' at amino acid positions 67-72 in the third hypervariable region (HVR3) of DRbeta. We aimed to identify the specific HLA alleles that are susceptible to type 1 AIH in Koreans, and to validate the shared epitope hypothesis in this single ethnic group.


METHODS
Sixty-two adult patients with definite type 1 AIH and 154 healthy controls were enrolled. Alleles of HLA class I and II genes were genotyped using sequence-based typing.


RESULTS
By high-resolution analysis, the frequencies of DRB1 *0405 and DQB1 *0401 were significantly increased in patients with AIH (P = 0.0001, OR = 3.74; P = 0.00006, OR = 3.95, respectively). The six amino acid motif represented by the single letter code LLEQRR or LLEQKR at positions 67-72 of the DRbeta polypeptide was not sufficient to show an increased risk for the disease. Interestingly, the QRRAA motif at positions 70-74 was significantly increased in Korean patients (P=0.04, OR=1.84).


CONCLUSIONS
The shared epitope hypothesis may be extended to the amino acid motif at positions 70-74 of HLA-DRbeta in order to better predict the susceptibility to type 1 AIH.
Lim
Young-Suk
YS
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Oh
Heung-Bum
HB
Choi
Sung-Eun
SE
Kwon
Oh-Joong
OJ
Heo
Yong-Seok
YS
Lee
Han Chu
HC
Suh
Dong Jin
DJ
D000328:Adult; D000368:Aged; D000483:Alleles; D000595:Amino Acid Sequence; D000939:Epitopes; D005260:Female; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D019693:Hepatitis, Autoimmune / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D007723:Korea / Q000453:epidemiology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk
D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains