Distribution of Major Histocompatibility Complex Alleles in Cohorts of Patients with Different Levels of Post-­Vaccination Antibodies against Hepatitis B

Abstract

Relevance. It is known that the immune response to the administration of immunobiological drugs is variable and depends on the individual characteristics of the organism. Host immunogenetic factors have a significant impact on the effectiveness of vaccination. In this study, the frequencies of alleles of the HLA class I (HLA-A, B, C) and class II genes (HLA-DRB1, DPB1, DQB1) were studied in groups of participants with different levels of antibodies (anti-HBs) after vaccination against viral hepatitis B. Aims of the work was to determine the possible relationship between alleles of HLA genes and the intensity of post-vaccination immunity against hepatitis B. Materials and methods. The study included 271 apparently healthy adults who were divided into 3 groups depending on the specific concentration of post-vaccination antibodies (anti-HBs) using ELISA. All calculations were made relative to the groups anti-HBs >100 mIU/ml (n=82), 10-100 mIU/ml (n=98) (protective antibody level) and anti-HBs <10 mIU/ml (n = 91). To type alleles of the HLA class I (HLA-A, B, C) and class II (HLA-DRB1, DPB1, DQB1) genes, we used a panel we developed for whole-genome next-generation sequencing (NGS). Statistical analysis was performed using Pearson's χ2 goodness-of-fit test using the FDR multiple correction method with an initial target of p < 0.05. Results. When typing the six genes studied, the total number of alleles identified at least once was 189 variants that were distinct from each other. We identified 3 alleles (B*38:01:01, DQB1*06:03:01 and DRB1*13:01:01), which were significantly more common (FDR p < 0.05) in the group with a protective level of anti-HBsS. Also in this group there was an increased frequency of occurrence of alleles A*26:01:01, A*32:01:01, C*12:03:01, DPB1*04:01:01 and haplotypes DQB1*06:03:01 -DRB1*13:01:01 and B*38:01:01-C*12:03:01. In the group of seronegative patients, alleles A*02:01:01, A*03:01:01, B*44:02:01, B*44:27:01, C*07:04:01, DPB1*04 were more common :01:01, DQB1*05:01:01, DRB1*01:01:01 and DRB1*16:01:01. It was shown that the identified associations were more significant in the group of individuals with a concentration of post-vaccination anti-HBs above 100 mIU/ml. Conclusion. The results obtained indicate that the HLA alleles we identified may influence the level of anti-HBsS production, and that the genetic factor may, to a greater extent, determine whether the antibody level exceeds 100 mIU/ml. defined as an anti-HBS level of 10 mIU/ ml. The development of an integrated approach to the organization of vaccine prevention, including the determination of genetic markers, will improve the quality of immunization of the population. Information about the association of HLA gene alleles can be used to develop predictive scenarios for the development of the hepatitis B epidemic process.

Keywords

• hla
• hbv
• hepatitis b
• post-vaccination immunity
• hbsag