Resequencing of the entire HLA region in autoimmune liver diseases

我们调查了日本自身免疫性肝炎（AIH）和原发性胆汁性肝硬化（PBC）患者的HLA I类A、B和C以及HLA II类DRB 1和DQB 1等位基因和单倍型。HLA-DRB 1 DRB 1 *04：05-DQB 1 *04：01单倍型与AIH易感性显著相关。相反，DRB 1 *15：01-DQB 1 *06：02单倍型与预防两种疾病发作相关。发现DRB 1 *08：03-DQB 1 *06：01与PBC易感性显著相关。DRB 1 *13：02-DQB 1 *06：04和DRB 1 *11：01-DQB 1 *03：01单倍型具有显著的保护性关联。DRB 1 *08：03-DQB 1 *06：01单倍型的频率在发生肝功能衰竭的AIH患者中显著较高。DRB 1 *09：01-DQB 1 *03：03单倍型在接受原位肝移植的PBC患者中的频率显著较高。我们在日本人群中建立了HLA单倍型在确定AIH和PBC易感性、保护和进展中的作用。

We investigated HLA class I A, B, and C and HLA class II DRB1 and DQB1 alleles and haplotypes in Japanese patients with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). HLA-DRB1 DRB1*04:05-DQB1*04:01 haplotype was significantly associated with AIH susceptibility. Conversely, the DRB1*15:01-DQB1*06:02 haplotype was associated with protection from both disease onset. Significant associations were found with PBC susceptibility for the DRB1*08:03-DQB1*06:01. There were significant protective associations with the DRB1*13:02-DQB1*06:04 and DRB1*11:01-DQB1*03:01 haplotypes. The frequency of the DRB1*08:03-DQB1*06:01 haplotype was significantly higher in AIH patients who developed hepatic failure. The frequency of the DRB1*09:01-DQB1*03:03 haplotype was significantly higher in PBC patients who had received orthotopic liver transplantation. We established the role of HLA haplotypes in determining AIH and PBC susceptibility, protection and progression in the Japanese population.