冈比亚地区一种MHC II类等位基因与乙肝病毒清除之间的关联

Association between an MHC class II allele and clearance of hepatitis B virus in the Gambia.

作者信息

Thursz M R, Kwiatkowski D, Allsopp C E, Greenwood B M, Thomas H C, Hill A V

机构信息

Academic Department of Medicine, St. Mary's Hospital Medical School, Imperial College, London, United Kingdom.

出版信息

N Engl J Med. 1995 Apr 20;332(16):1065-9. doi: 10.1056/NEJM199504203321604.

DOI:10.1056/NEJM199504203321604

PMID:7898524

Abstract

BACKGROUND

The course of hepatitis B virus (HBV) infection does not appear to be determined by variations in viral virulence and may be influenced by the host immune response. We studied the distribution of human leukocyte antigens in children and adult men in the Gambia who spontaneously recovered from HBV infection as compared with the distribution of these antigens in subjects with persistent infection.

METHODS

In a two-stage, case-control study, we analyzed the frequency of MHC class I antigens and class II haplotypes in people with either transient or persistent HBV infection. MHC class I typing was performed by microlymphocytotoxicity assays. MHC class II typing was performed with analysis of restriction-fragment-length polymorphisms (RFLPs), supplemented by other techniques.

RESULTS

In the first stage (the study of children up to the age of 10 years), the RFLP pattern 25-1, which includes the class II allele HLA-DRB11302, was found in 58 of 218 subjects with transient HBV infection (26.6 percent) and 30 of 185 subjects with persistent infection (16.2 percent) (relative risk of carrying the 25-1 pattern in the persistently infected group as compared with the transiently infected group, 0.53; 95 percent confidence interval, 0.32 to 0.90; P = 0.012). In the second stage (the study of adults), HLA-DRB11302 was found in 50 of 195 subjects with transient HBV infection (25.6 percent) and in 3 of 40 subjects with persistent infection (7.5 percent) (relative risk, 0.24; 95 percent confidence interval, 0.04 to 0.80; P = 0.012). The RFLP pattern 13-2, which includes the class II allele DRB1*1301, was less frequent in children with persistent infection than in those with transient infection, an association that was neither confirmed nor excluded by the data on adults. Possible associations with HLA class I antigens found in children were not supported by the data on adults.

CONCLUSIONS

The MHC class II allele DRB1*1302 was associated with protection against persistent HBV infection among both children and adults in the Gambia.

摘要

背景

乙肝病毒（HBV）感染的病程似乎并非由病毒毒力的变异所决定，可能受宿主免疫反应影响。我们研究了冈比亚自发从HBV感染中康复的儿童及成年男性中人类白细胞抗原的分布情况，并与持续感染患者中这些抗原的分布作比较。

方法

在一项两阶段病例对照研究中，我们分析了短暂或持续HBV感染人群中MHC I类抗原和II类单倍型的频率。MHC I类分型通过微量淋巴细胞毒性试验进行。MHC II类分型采用限制性片段长度多态性（RFLP）分析，并辅以其他技术。

结果

在第一阶段（对10岁以下儿童的研究），218例短暂HBV感染患者中有58例（26.6%）出现包含II类等位基因HLA - DRB11302的RFLP模式25 - 1，185例持续感染患者中有30例（16.2%）出现该模式（持续感染组携带25 - 1模式的相对风险与短暂感染组相比为0.53；95%置信区间为0.32至0.90；P = 0.012）。在第二阶段（对成年人的研究），195例短暂HBV感染患者中有50例（25.6%）出现HLA - DRB11302，40例持续感染患者中有3例（7.5%）出现该等位基因（相对风险为0.24；95%置信区间为0.04至0.80；P = 0.012）。包含II类等位基因DRB1*1301的RFLP模式13 - 2在持续感染儿童中比在短暂感染儿童中出现频率更低，这一关联在成人数据中未得到证实也未被排除。儿童中发现的与HLA I类抗原的可能关联在成人数据中未得到支持。