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同种异体肝移植受者中巨细胞病毒感染与人类白细胞抗原基因型的关联

Association of cytomegalovirus infection with human leukocyte antigen genotypes in recipients after allogeneic liver transplantation.

作者信息

Fan Jun, Meng Xue-Qin, Yang Mei-Fang, Zhou Lin, Chen Xiao-Ming, Hu Min-Jun, Fan Wei-Wei, Ma Wei-Hang, Li Lan-Juan

机构信息

Key Laboratory of Viral Infectious Diseases, Ministry of Public Health, Institute of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.

出版信息

Hepatobiliary Pancreat Dis Int. 2006 Feb;5(1):34-8.

Abstract

BACKGROUND

Cytomegalovirus (CMV) infection is the important cause affecting the survival rate and function of the transplanted organ after transplantation. The occurrence of CMV infection after liver transplantation (LT) is associated with many factors. Lots of studies suggest that genetic mutation between hosts and CMV may play a role in the occurrence and development of CMV infection. CMV exists in an incubative state, affect or destroy the expression of human leukocyte antigen (HLA) molecules in the host cell surface, and interfere antigen's submission. This mechanism is the key of CMV to avoid immune defense mechanism of the host. To detect HLA and CMV antibody (CMV-Ab), CMV antigen (CMV-Ag) of transplantation recipients, we evaluated the association of CMV infection and the particular HLA genotypes in recipients after LT.

METHODS

277 blood samples were collected from 39 LT recipients. CMV antibody and antigen were detected by ELISA or immunohistochemical methods. The HLA types of the recipients were determined by PCR. To analyze the association of HLA alleles and the occurrence of CMV antigenemia in the patients, relative risk degree (RR) was used as the parameter for the Chi-square test.

RESULTS

The LT recipients were serum CMV IgG positive (100%), but none of them was CMV IgM positive (0%). Thirty-three LT recipients (84.6%) were CMV antigenic positive with 1-50 positive leukocytes per 50,000 leukocytes in extent and 7.2+/-4.2 positive leukocytes per 50,000 leukocytes on average. Thirteen patients developed CMV pneumonia, with CMV antigenic positive (100%) and 17.7+/-5.5 positive leukocytes per 50,000 leukocytes on average. Some HLA alleles were associated with the occurrence and extent of CMV antigenemia. HLA-A2 was the higher frequency allele for patients with antigenemia (P<0.05), and 7 patients carrying HLA-DR11 allele developed antigenemia (P<0.05). In the lower antigenemia group, HLA-A11 was higher in frequency than others (P<0.05). Besides, none of the patients carrying HLA-B16 allele developed clinical symptoms of CMV infection (P<0.05).

CONCLUSIONS

The variability of HLA alleles might modulate immune response to CMV infection. HLA examination before transplantation should be made for prevention and treatment of CMV infection after operation.

摘要

背景

巨细胞病毒(CMV)感染是影响移植后器官存活率及功能的重要原因。肝移植(LT)后CMV感染的发生与多种因素相关。大量研究表明,宿主与CMV之间的基因突变可能在CMV感染的发生发展中起作用。CMV以潜伏状态存在,影响或破坏宿主细胞表面人类白细胞抗原(HLA)分子的表达,并干扰抗原呈递。这一机制是CMV逃避宿主免疫防御机制的关键。为检测移植受者的HLA及CMV抗体(CMV-Ab)、CMV抗原(CMV-Ag),我们评估了LT术后受者中CMV感染与特定HLA基因型的相关性。

方法

从39例LT受者中采集277份血样。采用ELISA或免疫组化方法检测CMV抗体和抗原。通过PCR确定受者的HLA类型。为分析HLA等位基因与患者CMV抗原血症发生的相关性,采用相对危险度(RR)作为参数进行卡方检验。

结果

LT受者血清CMV IgG均为阳性(100%),但CMV IgM均为阴性(0%)。33例LT受者(84.6%)CMV抗原阳性,每50000个白细胞中阳性白细胞数为1 - 50个,平均每50000个白细胞中有7.2±4.2个阳性白细胞。13例患者发生CMV肺炎,CMV抗原均为阳性(100%),平均每50000个白细胞中有17.7±5.5个阳性白细胞。一些HLA等位基因与CMV抗原血症的发生及程度相关。HLA-A2是抗原血症患者中频率较高的等位基因(P<0.05),7例携带HLA-DR11等位基因的患者发生了抗原血症(P<0.05)。在低抗原血症组中,HLA-A11的频率高于其他等位基因(P<0.05)。此外,携带HLA-B16等位基因的患者均未出现CMV感染的临床症状(P<0.05)。

结论

HLA等位基因的变异性可能调节对CMV感染的免疫反应。移植前应进行HLA检测以预防和治疗术后CMV感染。

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