| OBJECTIVE: â‘ Study the association between HLA-DR phenotype and intrauterine transmission of hepatitis B virus to probe into the susceptibility to intrauterine infection of hepatitis B virus.â‘¡ follow up the Hepatitis B immunized children born to HBsAg positive mothers. Observe the efficacy of vaccine and analyze the factors that caused failure of immunoprophylaxis. Detect the mutant probably existed in Taiyuan area and discuss the academic and realistic significance of HBV S mutant.METHODS: Newborns of HBsAg positive mothers birthed in Taiyuan infectious hospital were selected and following studies were conducted. â‘ By simple random sampling, 20 newborns had intrauterine infection of HBV or not were selected respectively. HLA-DR genotyping was conducted with PCR-SSP. The frequency of HLA-DR phenotype and difference between two groups were analyzed. â‘¡ After delivery, newborns were injected HBIG and accepted a standard course of immunization with HBV gene recombinant hepatitis B vaccine. These children were followed by letter and investigated face to face. Collect 2ml blood from elbow vein. HBsAg , HBeAg and anti-HBs were detected with ELISA. ALT was detected with R-F. HBVDNA was detected with nPCR. The positive rate of anti-HBs and the protective rate of vaccine were Computed. Risk factors related to hepatitis B vaccine failure were analyzed. PCR products from HBVDNA positive cases was sequenced after linking with pGEM T vector transforming Escherichia coli,identifying clones to detect mutants that was reported andpossible new.RESULTS: â‘ The frequency of DR3, DR51 in infection group(45%,40%) is higher than in un-infection group(20%,15%). OR is 3.27(0.67-17.08 ) , 3.78(0.69-23.02) respectively. The frequency of DR53 in un-infection group (60%) is higher than in infection group (35%). OR is 0.36(0.08-1.54). None of differences are significant. â‘¡44 children born to HBsAg positive mother were followed up. The positive rate of anti-HBs is 68.2%(31/44); the protective rate of vaccine is 50%(22/44). The HBV high infectivity of mother' blood during pregnant and intrauterine infection of HBV are risk factors to failure of hepatitis B vaccine. OR of HBeAg, HBVDNA to failure of vaccine is 3.85(1.11-13.30), 3.75(1.10-13.79) respectively, P is 0.03, 0.04 respectively. OR of intrauterine infection to anti-HBs negative and failure of vaccine is 4.32(1.14-6.40), 3.75(1.10-12.79). Strata analyzing showed that the direction of ORMH is unstable. The association between Breast-feeding and efficacy of vaccine is not significant. Analytical results of sequence isolated from seven children and one mother showed: Genotype and subtype of one case is B and adw, the other are C and adr. The homogeneity between eight sequences ranges from 94.0% to 99.6%. Eight cases have mutation from adenine (A) to cytosine (C) in 546th nucleotide and from asparagine (N) to threonine (T) in 131st amino acid residue. Seven cases have mutation from adenine (A) to thymine (T) in 636th nucleotide and from Tyrosine (Y) to phenylalanine (F) in 161 amino acid residue, except the forth sample. One case has mutation from guanine (G) to adenine (A) in 516th nucleotide and from cysteine (C) to tyrosine (Y) in 121st amino acid residue. Another case has mutation from thymine (T) to cytosine (C) in 552nd nucleotide and from methionine (M) to threonine (T) in 133rd amino acid residue. Other mutations in nucleotide are nonsense mutation.CONCLUSIONS: â‘ It is possible for DR3 , DR51 to be the phenotype susceptive to intrauterine infection of HBV and DR53 to be the protective phenotype. But further study including more samples is necessary to identify this relationship. â‘¡ The lower protective rate of vaccine may be related to population , time and adopting nPCR technique. High infectivity of mother' blood during pregnant and intrauterine infection of HBV are risk factors to failure of hepatitis B vaccine. It is unclear that if the HBV high infectivity is confounder factor to relationship betwee...
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