B和C基因型HBsAg^+/HBsAb^+双阳性患者S区基因的抗原表位及相关基因的突变

S region gene epitope and gene mutation of HBs Ag and HBs Ab coexistence patients with genotype B and C

目的探讨B和C基因型的乙型肝炎表面抗原(HBsAg)^+/乙型肝炎表面抗体(HBsAb)+双阳性乙型肝炎患者S区基因抗原表位之间的差异及其与HBsAg^+/HBsAb^+双阳性现象之间的关系。方法选取5例HBsAg^+/HBsAb^+双阳性样本的51个S区克隆株作为研究对象,对其S区基因克隆测序并进行统计分析。结果 5例样本中C基因型3例,B基因型2例。C基因型的30个克隆株S区氨基酸变异率显著高于B基因型的21个克隆株,且在S区的N端、C端及MHR区均存在差异。C基因型样本的变异位点主要分布在194、68、3位点,B基因型样本的变异位点则集中在40、200、129、5位点。结论不同基因型的HBsAg+/HBsAb+双阳性乙型肝炎患者在S区内的氨基酸变异存在差异,主要表现为变异位点及频次的不同,提示不同基因型的HBsAg可能具有不同的抗原表位,即只有抗原表位区内的氨基酸序列改变方可导致HBsAg抗原性改变,从而使HBsAg不能被HBsAb中和,易出现HBsAg^+/HBsAb^+双阳性现象。

Objective To investigate the difference between S region gene epitope and gene mutation of hepatitis B surface antigen （HBsAg） and hepatitis B surface antibody （HBsAb） coexistence patients with genotype B and C,and to study the correlation of HBsAg and HBsAb coexistence. Methods A total of 5 HBsAg and HBsAb coexistence patients were enrolled,and 51 S region clones were collected. S regions were amplified and sequenced. Result There were 3 patients with genotype C and 2 patients with genotype B. The amino acid mutation rate in S region of 30 clones with genotype C was higher than that of 21 clones with genotype B,and differences were found in S region N-terminal,C-terminal and major hydrophilic region（MHR）. The mutation loci of clones with genotype C were mainly concentrated in locus 194,68 and 3,while the mutation loci of clones with genotype B were mainly concentrated in locus 40,200,129 and 5. Conclusions There is difference in amino acid mutation in S region among HBsAg and HBsAb coexistence patients（mutation loci and frequencies） between different genotypes,so epitopes with different genotypes are different. Amino acid mutations within epitope region could lead to the antigenicity changes of HBsAg and potential subsequent failure of neutralization by HBsAb,leading to the coexistence of HBsAg and HBsAb.