儿童EBV阳性淋巴瘤miRNA表达的研究进展

EBV（Epstein-Barrvirus）感染是全球性普遍问题,文献报道EBV感染除与传染性单核细胞增多症、EB病毒相关噬血细胞综合征（Epstein—Barrvirus-associated lymphohistiocytosis hemophagocytic,EBV—HLH）、非洲伯基特淋巴瘤（Burkitt lymphoma,BL）、鼻咽癌和霍奇金淋巴瘤（Hodgkin’s lymphoma,HL）密切相关外,     

EB病毒感染相关性疾病

EB病毒(EBV)是已知的8个人类疱疹病毒之一。自1958年Burkitt首次报道Burkitt淋巴瘤及1964年Epstein和Barr在Burkitt淋巴瘤标本的体外传代细胞中发现EBV以来,已有多种疾病被证实与EBV感染有关,现综述如下。     

EB病毒相关恶性肿瘤研究进展

EB病毒（Epstein-Barrvirus，EBV）属疱疹病毒科γ亚科中惟一能引起人类感染的淋巴滤泡病毒，近50年来的研究证明EBV与淋巴瘤、白血病、移植后淋巴增生性疾病、鼻咽癌、胃癌等多种人类肿瘤发生有关。由于EBV对人类的普遍易感性，近年有关EBV的免疫学特性、逃避机体免疫应答的机制、EBV感染相关疾病的致瘤机制以及治疗方法等研究有了很大进展，本文就相关问题进行阐述。     

EBV-DNA检测在血液肿瘤性疾病中的应用价值

EB病毒 (EBV)属人类疱疹病毒 ,与人类多种疾病相关联。目的 　本研究探讨EB病毒感染与恶性血液病的关系。方法 　应用PCR法检测 38例血液肿瘤性疾病患儿骨髓细胞EBV -DNA。结果38例患儿骨髓EBV -DNA阳性检出率 6 1 % ( 2 3/38)。5例恶性淋巴瘤患儿均为阳性 ,急性白血病 (AL)、骨髓增生异常综合征 (MDS)、再生障碍性贫血 (AA)、特发性血小板减少性紫癜 (ITP)患儿阳性率较高 ,其余病例均为阴性。对照组 1 0例非血液病发热患儿仅 1例阳性。结论 　EBV感染与血液肿瘤性疾病的发生、发展及愈后关系密切。EBV感染可促使病情恶化或难治。同时对伴有不明原因发热的患儿除考虑肿瘤性发热外 ,应警惕因免疫功能异常导致的EBV易感因素 ,尽早动态检测EBV -DNA ,及时合理治疗。由于病人免疫力低下 ,对EBV病毒的免疫应答功能降低 ,抗体反应法作EBV常造成假阳性结果。本方法简便、快速、特异、敏感 ,具有重要的临床应用价值。     

儿童NK/T细胞淋巴瘤与survivin基因的表达

NK／T细胞淋巴瘤(NK／T cell lymphoma)是一种少见的结外原发性非霍奇金淋巴瘤,是与EB病毒(Epstein-Barrvirus,EBV)相关的具有高度侵袭性的恶性肿瘤。survivin是凋亡抑制蛋白(inhibitor of apoptosis proteins,IAP)家族的新成员,主要通过抑制caspase-3、caspase-7的活性而发挥抗凋亡作用。我们采用原位杂交技术检测EBV编码的RNA(EBERl／2),免疫组织化学技术检测survivin基因和EBV潜伏膜蛋白(LMP-1)表达,     

重症EB病毒感染相关疾病的现状和诊治进展

Epstein—Barr病毒，简称EB病毒（EBV），属于疱疹病毒，γ亚科，通过唾液的接触在人群中传播。该病毒被发现至今已有40多年的历史了。因其感染的普遍性及感染后终生潜伏而不能被机体免疫系统彻底清除，所以被称为“无处不在的成功病毒”。发展中国家2岁以下儿童EBV血清阳性转化率可达95％以上，由此可见一斑。在如此高的EBV血清阳性转化率下，大多数个体以“无症状”亚临床状态存在。对EBV致病性的认识，从最早的传染性单核细胞增多症（infectious mononucleosis，IM）到非洲高发的伯基特淋巴瘤，     

EB病毒原发性感染研究进展

EB病毒（Epstein—Barr virus，EBV）是Epstein和Barr于1964年首次用电镜在非洲儿童Burkitt淋巴瘤细胞中观察到的疱疹病毒样颗粒4年后EBV被确定为传染性单核细胞增多症的病原体。EBV属于疱疹病毒属γ亚科，是一种常见的人类疱疹病毒，具有嗜B细胞性，人群普遍易感，约有90％的成人血清中可检测到EBV阳性抗体，感染后为终生携带病毒。EBV感染在发展中国家的发病高峰年龄为2～6岁，在发达国家则多见于青少年，     

EB病毒相关性肿瘤疾病

EB病毒(EBV)是一种能诱发肿瘤的疱疹病毒.近年来,有关EBV在人体内生存的机制、感染后的免疫调控、相关疾病的发病机制等方面均有了新的认识.现就近年来EBV相关性肿瘤的研究进展情况进行介绍.     

儿童NK/T细胞淋巴瘤的免疫表型及其与EB病毒的关系

目的探讨儿童NK/T细胞淋巴瘤的免疫表型特征及其与EB病毒（EBV）感染的关系。方法NK/T细胞淋巴瘤5例标本,采用免疫组织化学链霉素抗生物素-过氧化酶连接法（SP法）检测CD45RO、CD3ε、CD56、CD20、T细胞内抗原（TIA-1）、丝氨酸蛋白酶-粒酶B（Granzyme B）确定肿瘤细胞免疫表型及EBV潜伏膜蛋白（LMP-1）,原位杂交技术检测EBV编码的RNA（EBER1/2）。结果NK/T细胞淋巴瘤5例CD45RO、CD3ε、TIA-1和Granzyme B全部阳性,CD56阳性2例,CD20全部阴性。EBER1/2阳性4例,LMP-1阳性3例。结论EBV感染与儿童NK/T细胞淋巴瘤关系密切,EBV感染在儿童NK/T细胞淋巴瘤的发生发展中可能起重要作用。     

EB病毒感染与Burkitt淋巴瘤

<正>EB病毒(Epstein-Barr virus,EBV)是一种嗜人类B淋巴细胞的γ疱疹病毒,它与淋巴瘤、鼻咽癌等多种人类肿瘤发生有关[1]。Burkitt淋巴瘤是一种侵袭性B细胞恶性淋巴瘤,有研究提出EBV在Burkitt淋巴瘤发生中起着重要作用[2-3]。现就EBV感染、Burkitt淋巴瘤及两者之间关系的研究作一综述。     

From Burkitt's lymphoma to chronic active Epstein-Barr virus (EBV) infection: an expanding spectrum of EBV-associated diseases

Epstein-Barr virus (EBV) is one of 8 known human herpesviruses. EBV infection usually occurs in early childhood and is subclinical. However, primary infection in adolescence or adulthood causes infectious mononucleosis in approximately half of infected individuals. Recently, the spectrum of human diseases associated with EBV infection has increased, primarily due to methodological advances in EBV detection. Initially, EBV was isolated from a cultured Burkitt lymphoma cell line, and has been felt to be etiologically linked to the development of Burkitt lymphoma, as well as other human malignancies. This review mainly focuses on pathogenetic mechanisms, many of which remain enigmatic, for the various human diseases, which are considered to be associated with EBV infection.     

FROM BURKITT'S LYMPHOMA TO CHRONIC ACTIVE EPSTEIN-BARR VIRUS (EBV) INFECTION: An Expanding Spectrum of EBV-Associated Diseases

Epstein-Barr virus (EBV) is one of 8 known human herpesviruses. EBV infection usually occurs in early childhood and is subclinical. However, primary infection in adolescence or adulthood causes infectious mononucleosis in approximately half of infected individuals. Recently, the spectrum of human diseases associated with EBV infection has increased, primarily due to methodological advances in EBV detection. Initially, EBV was isolated from a cultured Burkitt lymphoma cell line, and has been felt to be etiologically linked to the development of Burkitt lymphoma, as well as other human malignancies. This review mainly focuses on pathogenetic mechanisms, many of which remain enigmatic, for the various human diseases, which are considered to be associated with EBV infection.     

Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder

De novo malignancies represent an increasing concern in the transplant population, particularly as long-term graft and patient survival improves. EBV-associated B-cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell-based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B-cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV-associated malignancies.     

Epstein-Barr virus in pediatric Hodgkin disease: Age and histiotype are more predictive than geographic region

Epidemiologic studies have implicated Epstein-Barr virus (EBV) in the great majority (80%–100%) of Hodgkin disease (HD) cases in South American countries, versus only 30%–40% in the United States and other industrialized countries. Other EBV-related malignancies are known to be geographically localized, including nasopharyngeal carcinoma in south China and Burkitt lymphoma in equatorial Africa. Some studies, however, have suggested that age and histiotype, rather than geographic region, are the major determinants of the association between EBV and HD. To further characterize this relationship in children, we matched 26 cases of pediatric Hodgkin disease from south Brazil and 26 cases from the U.S.-for histiotype and age. The Brazilian children (22 males, 4 females) had a median age of 9 years, while the median age of the U.S. group (11 males, 15 females) was 7.5 years. Formalin-fixed, paraffin-embedded biopsy material was examined for EBV early RNA1 (EBER1) expression by in situ hybridization. This antigen was detected solely in Reed-Sternberg cells or their variants in positive samples. The same proportion of cases was positive (15/26 or 58%) in both groups of children. After adjustment for histiotype and age, the association between EBV and HD remained independent of geographic location, but was more frequent in children aged ≤ 10 years at diagnosis. These findings support the multiple-etiology hypothesis for Hodgkin disease. Med. Pediatr. Oncol. 28:248–254. © 1997 Wiley-Liss, Inc.     

Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients

A major risk faced by bone-marrow and solid organ transplant patients is the development of post-transplant lymphoproliferative disease or post-transplant lymphoma (PTLD). In pediatric transplantation, PTLD onset is often associated with a rapid rise in Epstein-Barr virus (EBV) load in peripheral blood mononuclear cells (PBMC). We have analyzed EBV viral loads in PBMC over time using real-time quantitative PCR in 56 patients, 19 of which have been followed for more than 1 year. In nine patients; eight bone marrow (BMT) and one kidney transplant, PTLD was associated with a rapid rise in viral load, exceeding 1 x 10(5) EBV genomes/microg of PBMC-derived DNA. Four of these patients exceeded 1 x 10(6) EBV genomes/microg PBMC DNA. All patients with viral loads exceeding 1 x 10(5) EBV genomes/microg PBMC DNA were clearly at high risk for transplant-associated mortality, with only six of nine surviving. Importantly, only one of these deaths was directly attributable to EBV. A second elevated state of EBV load, defined as exceeding 2 x 10(4) EBV genomes/microg PBMC, was seen in a total of 12 BMT, kidney, heart, and liver transplant patients. These patients did not appear to be at immediate lethal risk for PTLD and one EBV-attributable death was found in this group as well. Thirty-four transplant patients whose EBV viral load oscillated from undetectable to 10 000 EBV genomes/microg PBMC DNA are reported as well. The threshold for normal EBV viral load based on our combined experience with viral load analysis is defined as 1 x 10(4) EBV genomes/microg PBMC DNA. The ability to rapidly analyze EBV load allows rapid changes in viral load, such as those that occur with PTLD onset, and the impact of anti-CD20 antibody therapy to be rapidly detected.     

High prevalence of Epstein–Barr virus type A strain with the 30 b.p. deletion of the latent membrane protein-1 gene in a Japanese population

BACKGROUND: The pathogenic activity of Epstein-Barr virus (EBV) with a characteristic 30 b.p. deletion of the latent membrane protein-1 (LMP-1) gene is controversial. We analyzed the LMP-1 gene and two major strains of EBV, type A and type B, in Japanese patients with EBV-associated disease. METHODS: We directly sequenced the carboxy terminal part of the LMP-1 gene from 15 EBV-infected patients; 10 patients with infectious mononucleosis (IM) and one patient each with Hodgkin's disease, B cell lymphoma, Wiskott-Aldrich syndrome (WAS), AIDS and atypical EBV infection (atEBV). The EBV subtype was studied by determining the 3' divergence of Epstein-Barr virus nuclear antigen (EBNA)-2 using polymerase chain reaction primers. RESULTS: Twelve of 15 patients had EBV with the 30 b.p. deletion and numerous point mutations of the LMP-1 gene, regardless of the disease. Two patients, one with IM and one with WAS, had EBV without the 30 b.p. deletion. One patient with atEBV had two types of LMP-1 gene, one with and one without the 30 b.p. deletion. Thirteen patients had EBV type A, the WAS patient had the type B strain and the atEBV patient had both types A and B. In the patient with atEBV, the two types of LMP-1 gene and two EBV subtypes were detected simultaneously. CONCLUSIONS: The characteristic 30 b.p. deletion of the LMP-1 gene is not an important factor in the pathogenesis of EBV-associated diseases. The EBV type A strain with the 30 b.p. deletion of the LMP-1 gene is prevalent in the Japanese population.     

Detection of Epstein-Barr virus DNA in plasma and lymph node biopsy samples of pediatric and adult patients with Hodgkin lymphoma

Hodgkin lymphoma (HL) is commonly associated with latent Epstein-Barr virus (EBV) infection. The aim of this study is a molecular analysis of the EBV status in both involved lymph node biopsies and plasma samples of patients with HL. Plasma and lymph node biopsy samples obtained from 15 pediatric and 10 adult HL patients were examined for EBV DNA using conventional polymerase chain reaction (PCR). The control group consisted of 30 healthy pediatrics and adults. In addition, immunoglobulin G (IgG) anti-EBV nuclear antigen (EBNA)-1 antibody was determined in sera of patients and controls using enzyme-linked immunosorbent assay (ELISA). IgG Anti EBNA-1 antibody was detected in 21 (84%) and 8 (26%) of patients and controls, respectively (P < .05). EBV DNA was detected in 12 (48%) and 1 (3%) plasma samples of patient and control cases, respectively. Significant difference was observed in plasma DNA detection between patients and controls (P < .05). Comparison of EBV DNA detection in plasma and biopsy samples between children and adult patients was only significant for plasma samples (P = .025). Significant correlation was observed in positive detection of EBV DNA between plasma and biopsy samples of the same individual (P < .001, r = .923). Frequency of EBV DNA in plasma and biopsy samples obtained from mixed-cellularity subgroup was higher than the nodular sclerosis; however, no significant difference was observed between these 2 subgroups. EBV detection in plasma of childhood Hodgkin lymphoma in a population with EBV seroconversion might be of value as a biomarker for EBV-associated Hodgkin lymphoma.     

Epstein-Barr virus infection and associated diseases in children

Epstein-Barr virus (EBV), an ubiquitous human B lymphotropic virus, is the cause of infectious mononucleosis. Moreover, EBV infection can be followed by lymphoproliferative diseases in patients with inherited and acquired immunodeficiencies. Primary EBV infection may be a threat to all children after marrow or organ transplantation or those receiving chronic immunosuppressive treatment for various other reasons. The virus has been also implicated in the pathogenesis of different malignant tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease and some T-cell lymphomas. This review focuses on various aspects of virus-host interactions, immune mechanisms of the host, and the still experimental therapeutic approaches in EBV-associated diseases.     

Epstein-Barr virus infection and associated diseases in children

Epstein-Barr virus (EBV), an ubiquitous human B lymphotropic virus, is the cause of infectious mononucleosis. Moreover, EBV infection can be followed by lymphoproliferative diseases in patients with inherited and acquired immunodeficiencies. Primary EBV infection may be a threat to all children after marrow or organ transplantation or those receiving chronic immunosuppressive treatment for various other reasons. The virus has been also implicated in the pathogenesis of different malignant tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, Hodgkin disease and also some T-cell lymphomas. This review focuses on various aspects of virus-host interactions, immune mechanisms of the host, and the still experimental therapeutic approaches in EBV-associated diseases.     

X-连锁淋巴细胞异常增生症一例及其家系基因和蛋白表达研究

目的 探讨1例中国X-连锁淋巴细胞异常增生症(XLP)患儿及其家系的临床特征、基因突变和外周血单个核细胞(PBMC)SAP蛋白表达.方法 患儿男,6岁,于5岁时发现右腰部肿物,活检提示为伯基特淋巴瘤.其胞兄及表兄均于1岁左右因重症传染性单核细胞增多症夭折.据临床表现、家族史、免疫学特征拟诊为XLP.提取患儿及部分亲属基因组DNA,采用PCR法扩增SH2D1A基因,PCR产物直接进行双向序列测定,采用流式细胞仪检测PBMC中SAP蛋白表达.结果 患儿在缓解期EBV-DNA检测为536.9拷贝/ml(＞500拷贝/ml为EBV阳性),其SH2D1A基因第2外显子462位核苷酸发生无义突变,碱基C突变为T,形成TGA终止密码子(Arg55X),患儿母亲、姨母及外祖母为该突变携带者.患儿PBMC中SAP蛋白表达水平明显下降,而携带者SAP蛋白表达未见异常.结论 通过临床及实验室检查,确诊1例XLP患儿及家系.男性重症EBV感染,甚或无EB病毒感染证据,但具有家族史的淋巴瘤患儿应考虑XLP.SAP蛋白流式细胞仪检测为快速、准确的诊断手段.