Importance of HBsAg recognition by HLA molecules as revealed by responsiveness to different hepatitis B vaccines.

Autor: Nishida N; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan. nishida-75@umin.ac.jp., Sugiyama M; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Ohashi J; Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Bunkyo-ku, 113-0033, Japan., Kawai Y; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Khor SS; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Nishina S; Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama, 701-0192, Japan., Yamasaki K; Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, 856-8562, Japan., Yazaki H; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Okudera K; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Tamori A; Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, 558-8585, Japan., Eguchi Y; Division of Hepatology, Saga Medical School, Saga, 840-8502, Japan., Sakai A; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan.; Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8577, Japan., Kakisaka K; Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba-cho, 028-3694, Japan., Sawai H; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, 113-0033, Japan., Tsuchiura T; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Ishikawa M; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Hino K; Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama, 701-0192, Japan., Sumazaki R; Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8577, Japan., Takikawa Y; Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Yahaba-cho, 028-3694, Japan., Kanda T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.; Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Itabashi-ku, 173-8610, Japan., Yokosuka O; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, 260-8670, Japan.; Japan Community Health Care Organization Funabashi Central Hospital, Funabashi, 273-8556, Japan., Yatsuhashi H; Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, 856-8562, Japan., Tokunaga K; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan., Mizokami M; Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Mar 02; Vol. 11 (1), pp. 3703. Date of Electronic Publication: 2021 Mar 02.
DOI: 10.1038/s41598-021-82986-8
Abstrakt: Hepatitis B (HB) vaccines (Heptavax-II and Bimmugen) designed based on HBV genotypes A and C are mainly used for vaccination against HB in Japan. To determine whether there are differences in the genetic background associated with vaccine responsiveness, genome-wide association studies were performed on 555 Heptavax-II and 1193 Bimmugen recipients. Further HLA imputation and detailed analysis of the association with HLA genes showed that two haplotypes, DRB1*13:02-DQB1*06:04 and DRB1*04:05-DQB1*04:01, were significantly associated in comparison with high-responders (HBsAb > 100 mIU/mL) for the two HB vaccines. In particular, HLA-DRB1*13:02-DQB1*06:04 haplotype is of great interest in the sense that it could only be detected by direct analysis of the high-responders in vaccination with Heptavax-II or Bimmugen. Compared with healthy controls, DRB1*13:02-DQB1*06:04 was significantly less frequent in high-responders when vaccinated with Heptavax-II, indicating that high antibody titers were less likely to be obtained with Heptavax-II. As Bimmugen and Heptavax-II tended to have high and low vaccine responses to DRB1*13:02, 15 residues were found in the Heptavax-II-derived antigenic peptide predicted to have the most unstable HLA-peptide binding. Further functional analysis of selected hepatitis B patients with HLA haplotypes identified in this study is expected to lead to an understanding of the mechanisms underlying liver disease.
Databáze: MEDLINE
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