Analysis of Human Leukocyte Antigen Polymorphism with Outcomes of Hepatitis B virus Infection and the Immunologic Responses to Hepatitis B Vaccination

• Main Authors: Zong-Ying Wu, 吳宗盈
• Other Authors: Yuan-Soon Ho
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/92750938356307000192

碩士 === 臺北醫學大學 === 醫學科學研究所 === 97 === Following an acute hepatitis B virus (HBV) infection, spontaneously clearance or chronic carrier is determined by the host immune response. Vaccination is important in preventing hepatitis B infection. However, approximately 5-10% of vaccines were poor or no response to hepatitis B (HB) vaccine. Since the human leukocyte antigen system (HLA) is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes are key determinants of viral clearance and immune response to HB vaccine. Subjects in this study were participants into two studies: (i) the HBV infected study, we enrolled a total of 434 persons who had visited Medical Center for renal or heat transplantation, as either recipients or donors, between January 2001 and September 2007. Subjects were confirmed who have ever infected Hepatitis B virus history, and categorized into 2 different groups: the ‘‘Chronic Carrier Group’’ (CC), and ‘‘Spontaneously Cleared Group’’ (SC) according to the course of HBV infection. The “CC” group who had been hepatitis B surface antigen (HBsAg)-positive for at least 6 months. The “SC” group who was HBsAg-negative with antibodies to HBsAg (anti-HBs) and hepatitis B core antigen (anti-HBc). We excluded subjects who were HBsAg-negative and had anti-HBs, but not anti-HBc. (ii) the vaccination study were obtained from 121 persons (48 health care workers and 73 university students) who and before and after three dose of 20 ug/ml hepatitis B vaccine (Engerix B Hepatitis B Recombinant Vaccine). Each sample was assayed for HBs Ag, Anti-HBs and Anti-HBc using commercial available kits (VITROS ECi Immunodiagnostic System). DNA was extracted from 200 ul sample of blood by Viogene Blood and Tissue Genomic DNA Extraction Miniprep System. HLA-A, -B and -DR typing was performed using commercial PCR-reverse SSOP kits. (Dynal Bioteck Ltd. U.K). Chi-square and Fisher exact test was used to compare categorical variables as appropriate. A p less than 0.05 was considered statistically significant. In HBV infected subject, a total of 16 individuals fulfilled our criteria for a “CC” HBV infection and were matched to 70 individuals with “SC”. In vaccination subject, 121 persons who were HBV-naïve were enrolled After 3 doses of HB vaccination, 15 were nonresponders (Anti-HBs <10 mIU/ml) _with and the remaining 106 were responders (Anti-HBs ≥ 10 mIU/ml). HLA typing to HLA A, B and DR locus were undertaken using sequence-specific oligonucleotide probe hybridization. Compared to “SC”, the “CC” had significant increased frequency of HLA-DRB1*09 (28.13% versus 4.86%, OR=4.58, 95% CI: 1.53-13.68, p=0.003). Compared to responders, the non-responders had significant and marginally-significant increased frequency of HLA-B*55 (16.67% versus 4.72%, OR=4.04, 95% CI: 1.10-14.32, p=0.033), HLA DRB1*04 (36.37% versus 17.45%, OR=2.74, 95% CI 1.11-6.92, p=0.026). HLA-DRB1*09 allele be associated with the chronic HBV infection. The other hand, the HLA-B*55 and HLA DRB1*04 alleles be associated with the no responsiveness to hepatitis B vaccination. The possibility of association to other alleles could not be ruled out due to the limited sample size in this study.