Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation
Hepatitis B virus with antigenically altered hepatitis B surface antigen is selected by high-dose hepatitis B immune globulin after liver transplantation
复制标题
DOI：
10.1002/hep.510270138
复制
发表时间：
1998-01-01
期刊：
影响因子：
13.5
通讯作者：
Gerken, G
中科院分区：
文献类型：
--
作者：
Protzer-Knolle, U;Naumann, U;Gerken, G
尽管有过免疫接种，但乙肝病毒的“逃逸”变种仍可引起感染。这些病毒表现出乙肝病毒小表面蛋白(S蛋白)免疫原性主要亲水环的变化。我们研究了接受大剂量多克隆乙肝高免疫球蛋白(HBIG)被动免疫预防的肝移植术后感染的患者是否选择了乙肝病毒“逃逸”变异体。为此，对34例患者移植前后血清中HBVS基因变异的发生情况进行了分析。此外，还研究了体外翻译的S变异体蛋白与HBIG的结合。在HBIG过程中，A型HBV144个氨基酸(S144)和D型145个氨基酸(S145)的变异被发现出现、持续并占主导地位，因此符合所选“逃逸”变异的标准。除了已知的突变体sG145R/K/E外，我们还可以证明新描述的突变体sX144G和sG145A在体外发生了抗原性改变，并显示出多克隆HBIG的识别障碍。对变异S蛋白的认识减弱与HBIG未能预防肝移植感染有关。感染“逃逸”变异乙肝病毒变异体S144或S145的患者与其他接受高剂量、长期预防HBIG的患者相比，临床结果更差(44%比23%由乙肝病毒感染导致的移植失败)。我们的结果提示HBIG可以选择抗原改变的乙肝病毒变异株S144和S145，并且可以影响肝移植后的临床结果。
"Escape" variants of hepatitis B virus (HBV) can cause infection despite previous immunization. These viruses show alterations of the immunogenic major hydrophilic loop of the HBV small surface protein (s-protein). We studied whether HBV "escape" variants were selected in patients with graft infection after liver transplantation for HBV-related diseases who received passive immunoprophylaxis with high-dose polyclonal hepatitis B hyperimmune globulin (HBIG). For that, pre-and posttransplantation sera of 34 patients were analyzed for the occurence of HBV S-gene variants. In addition, binding of in vitro-translated variant s-proteins to HBIG was studied. Variants with exchanges of amino acid (aa) 144 (s144) in HBV genotype A and 145 in genotype D (s145) were found to emerge, persist, and predominate during HBIG, and thus fulfilled criteria of "escape" variants selected. In addition to already-known variants sG145R/K/E, we could demonstrate that newly described variants sX144G and sG145A were antigenically altered and showed impaired recognition by polyclonal HBIG in vitro. Diminished recognition of variant s-proteins correlated with the failure of HBIG to prevent infection of the liver graft with antigenically altered variant HBV Patients infected with "escape" variants s144 or s145 showed a worse clinical outcome compared with the other patients on high-dose, long-term HBIG prophylaxis (44% vs. 23% graft failure caused by HBV infection). Our results suggest that antigenically altered HBV variants s144 and s145 can be selected by HBIG and can influence clinical outcome after liver transplantation.