Novel HLA allele associations with susceptibility, staging, symptomatic state, autoimmune hepatitis and hepatocellular carcinoma events for primary biliary cholangitis in the Japanese population

• DOI: 10.3389/fimmu.2023.1151502
• Publication Date: 2023-05-31T05:21:30Z
• Authors: Seik-Soon Khor; Kazuko Ueno; Nao Nishida; Minae Kawashima; Yosuke Kawai; Yoshihiro Aiba; Yuki Hitomi; Masao Nagasaki; Minoru Nakamura; Katsushi Tokunaga
• Keywords: Autoimmune Hepatitis; HLA-DQB1; Genetic predisposition; Primary Biliary Cirrhosis

Primary biliary cholangitis (PBC) is a rare autoimmune disease with clear predisposition for human leukocyte antigen (HLA)-DR/DQ -associated loss of immune tolerance the E2 component pyruvate dehydrogenase complex. Three-field-resolution HLA imputation 1,670 Japanese PBC patients and 2,328 healthy controls was conducted using population-specific reference panels. Eighteen previously reported PBC-associated alleles were confirmed extended to 3-field-resolution, including HLA-DRB1*08:03 HLA-DRB1*08:03:02 , HLA-DQB1*03:01 HLA-DQB1*03:01:01 HLA-DQB1*04:01 HLA-DQB1*04:01:01 HLA-DQB1*06:04 HLA-DQB1*06:04:01 . In addition, additional significant novel identified, 3 susceptible HLA-DQA1 alleles: HLA-DQA1*03:03:01 HLA-DQA1*04:01:01 HLA-DQA1*01:04:01 1 protective allele, HLA-DQA1*05:05:01 carrying HLA-DRB1*15:01:01 would have higher toward developing concomitant hepatitis (AIH). Further, late-stage symptomatic shared same HLA-A*26:01:01 HLA-DRB1*09:01:02 HLA-DQB1*03:03:02 Lastly, HLA-DPB1*05:01:01 identified as potential risk allele development hepatocellular carcinoma (HCC) in patients. conclusion, we current knowledge associations 3-field resolution risk, staging, state, AIH HCC events