Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70–74 of the HLA-DRB1 molecule

Background/Aims 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 DRβ. 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 DRβ 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-DRβ in order to better predict the susceptibility to type 1 AIH.