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。     

EB病毒感染与淋巴增殖性疾病

EB病毒(EBV)是一种能诱发肿瘤的疱疹病毒.多数情况下,由于机体的免疫系统能严格限制病毒颗粒的增殖,受感染者终生携带病毒而不发病.少数情况下如机体免疫功能明显降低,则可引起严重的相关性疾病,特别是良性或恶性的淋巴增殖性疾病.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与淋巴增殖性疾病的有关进展情况进行介绍.     

原发性EB病毒感染后特异性T细胞免疫功能的研究进展

原发性EB病毒(EBV)感染后机体产生针对裂解期和潜伏期病毒抗原特异性CD8~+/CD4~+细胞毒性T细胞(CTL),清除病毒控制EBV感染.EBV原发感染后临床表现多样,造成这一现象的原因尚不明确,其特异性T细胞对控制病毒感染起到关键作用.随访研究发现EBV原发感染后针对裂解期和潜伏期病毒抗原特异性T细胞功能变化不同,同时对EBV特异性T细胞亚群的分析发现,T细胞的迁移活化在EBV感染机制中亦起到重要作用.     

EB病毒检测与EB病毒感染诊断的研究

目的 探讨EB病毒(EBV)检测在EBV感染诊断中的临床意义.方法 应用酶联免疫吸附方法 和荧光定量PCR方法 同步检测38例疑诊EBV感染患儿入院时及起病1、3、6、9个月血浆中EBV VCR-IgM及外周血全血、血浆、单个核细胞(PBMC)中EBV DNA,比较EBV感染患儿病程中4种检测方法 的检出率.结果 在疑诊EBV感染初期,全血和PBMC中EBV DNA阳性率最高,与EBV VCR-IgM及血浆EBV DNA相比,差异具有显著性(P<0.05);起病后的1、3、6及9个月,4种检出方法 的阳性率均逐渐减低,但PBMC中EBV DNA敏感性始终高于其他3种方法 .结论 EBV感染初期,检测全血和PBMC中EBV DNA是早期、快速、敏感的检测方法 ;EBV可长期存在于PBMC中,荧光定量PCR法检测外周血PBMC中EBV DNA对EBV感染的诊断有重要价值,可作为判断疗效及监测病情的一种有效手段.     

EB病毒亚型/变异株及其与疾病关系的研究进展

Epstein-Barr病毒(Epsteir-Barr virus,EBV)属于疱疹病毒科γ亚科,与鼻咽癌、地方性伯基特淋巴瘤和霍奇金淋巴瘤等相关,是重要的肿瘤相关病毒.EBV基因组中存在多个多态性区域,根据这些区域中氨基酸的变异,可将EBV分为不同的亚型/变异株.目前,关于不同EBV亚型/变异株与疾病间是否相关尚无定...     

急性淋巴细胞白血病并EB病毒感染的临床分析

目的 探讨EB病毒(EBV)在急性淋巴细胞白血病(ALL)儿童中的感染及其临床意义.方法采用荧光定量聚合酶链反应(FQ-PCR)技术检测EBV DNA,ELISA法检测EB病毒衣壳抗原IgM抗体(EBV-CA-IgM),共检测47例.其中新发45例,复发2例;年龄0～14岁[(8.06±3.71)岁].另取14例健康儿童作为健康对照组.男9例,女5例;年龄2～10岁[(7.24±2.54)岁].结合临床表现、诱导治疗骨髓完全缓解(CR)率、形态学CR状态下的微小残留病(MRD)、复发率及无事件生存(EFS)率等分析ALL患儿中EBV感染情况及其临床意义.结果 47例ALL患儿中检出EBV感染15例(31.9%),其中11例(23.40%)检出EBV DNA,EBV DNA水平为(3.28±5.95)×108copy·L-1;14例健康对照组外周血未检测到EBV DNA及EBV-CA-IgM.ALL中EBV感染组与非EBV感染组白细胞数分别为(78.00±58.38)×109 L-1、(27.46±60.10)×109 L-1(t=2.70,P=0.01),诱导治疗CR率分别为 46.7%、87.5%(P<0.01),MRD>10-3分别为90.0%、26.1%(P<0.01),复发率分别为53.8%、13.8%(P<0.01),EFS率分别为 23.1%、82.8%(P<0.01).结论 ALL并EBV感染具有高白细胞数、低诱导治疗CR率、高复发率、低EFS率,提示EBV感染可能参与儿童ALL的发生发展过程,亟待改善EBV感染ALL的治疗方法.     

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。     

慢性活动性EB病毒感染

慢性活动性EB病毒(EBV)感染主要表现为慢性或复发性传染性单核细胞增生症样症状,包括持续或间断发热、肝肿大、脾肿大、肝功能异常、血小板减少症、蚊虫叮咬过敏、皮疹等;表现有外周血高EBV载量和(或)异常的EBV相关抗体.该病临床少见但病死率极高,发病机制目前尚不清楚,新的诊断指南正在研究提出.传统的抗病毒治疗效果有限,新的治疗措施包括免疫抑制剂、免疫调节治疗、免疫细胞治疗等.     

EB病毒感染的免疫机制研究进展

<正>1 EB病毒(EBV)的生物学特点EBV,又称人类疱疹病毒4型,类似于其他疱疹病毒,EBV基因组为双链线性DNA分子,是第一个被发现与人类肿瘤有关的DNA病毒。EBV在全球范围内感染率90%。EBV基因组具有高度的变异性,不同的变异体的致病力和分布不同。根据EBV核抗原(EBNA),主要是EBNA2和EBNA3A、-B、-C基因序列的不同,将EBV分为1型和2型~([1])。在西方和东南亚等国家EBV 1型多见,在非洲EBV两型均多见~([2])。     

儿童EB病毒相关噬血细胞综合征的分子生物学机制和诊疗研究进展

EB病毒相关噬血细胞综合征起病凶险,进展迅速,预后差,未经治疗者病死率高.其具体发病机制目前尚不完全清楚,可能与SH2D1A基因突变和EBV潜在膜蛋白1有关.诊断首先需符合噬血细胞性淋巴组织细胞增多症诊断标准,并存在EB病毒感染证据,同时排除原发性噬血.治疗上首选联合化疗,若化疗效果不佳,可行造血干细胞移植和单克隆抗体治疗.     

Virus-associated immune thrombocytopenic purpura in childhood

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immunodeficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, Ihsan Dogramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELlSA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.     

VIRUS-ASSOCIATED IMMUNE THROMBOCYTOPENIC PURPURA IN CHILDHOOD

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immuno deficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, &#71 hsan Do &#60 ramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELISA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.     

Epstein-Barr virus DNA in lymphocytes of patients with the virus-associated hemophagocytic syndrome

The virus-associated hemophagocytic syndrome (VAHS) is a histiocytic proliferative disorder with bone marrow and liver failure for which the connection with a specific virus is often tenuous. Epstein-Barr virus (EBV) is one candidate for the association, but serologic or culture confirmation may be lacking in a particular case. As a means of directly identifying the presence of EBV in patients' cells, molecular hybridization studies were carried out using a radioactively labeled viral DNA segment. DNA from mononuclear cells of two children with VAHS had specific hybridization to the EBV DNA probe. One of the patients had serologic evidence for EBV infection. Several immunologic deficiencies were found. VAHS may represent one of several hematologic and/or immunologic dysfunctions caused by EBV.     

Characteristic MR features of encephalitis caused by Epstein-Barr virus: a case report

An 8-year-old girl showed symptoms of encephalitis during acute Epstein-Barr virus (EBV) infection. The diagnosis of EB virus infection was made by changes in the titres of EB virus-specific antibody. Cranial MRI demonstrated abnormal low and high signal intensities in the striatal body (putamen and caudate nucleus) on T1-weighted and T2-weighted images, respectively, during the acute phase. These abnormal findings had almost completely resolved 1 month later. EBV infection should be considered when lesions are localised to the basal ganglia. Received: 5 May 1997 Accepted: 6 February 1998     

Effect of Interferon-α Therapy in a Patient with Common Variable Immunodeficiency and Chronic Epstein-Barr Virus Infection

We report an 18-year-old boy with common variable immunodeficiency who presented with splenomegaly as well as left axillary and lateral cervical lymphadenopathy. Main laboratory investigations showed severe thrombocytopenia. Epstein-Barr virus (EBV) DNA was delected in the patient's throat-washing specimens and lymph node biopsy. Lymphocytes from the lymph node biopsy were also positive for EBV nuclear antigen. Serology for EBV and cytomegalovirus was negative. A therapeutic attempt with acyclovir did not influence the course of infection. Six months' treatment with human lymphoblastoid interferon-α (IFN alfa) brought about the normalization of clinical and hematologic conditions. Detection on throat-washing specimens carried out 1 year after therapy was negative. Our preliminary experience suggests that human lymphoblastoid IFN-α is a valid alternative in therapy of immunodeficient EB virus-infected patients.     

Kawasaki disease with a concomitant primary Epstein-Barr virus infection

A two year old boy exhibited not only clinical manifestations which suggested a recurrence of Kawasaki disease (KD) but also evidence of a primary infection by Epstein-Barr virus (EBV) including tonsillitis, splenomegaly and atypical lymphocytosis in the peripheral blood. An inverted CD4/CD8 ratio in lymphocyte subsets suggested the presence of infectious mononucleosis (IM). Epstein-Barr virus titers (viral capsid antigen-immunoglobulin G 1:20; Epstein-Barr virus-associated nuclear antigen < 1:10) showed an acute EBV infection and the presence of EBV genome in the blood was determined by the polymerase chain reaction technique. In Japan, the peak incidence of KD and IM is in children under 4 years of age. From the investigation of EBV titers, it has been reported that some patients with KD develop an associated, unusual primary EBV infection. Kawasaki disease concurrent with a primary EBV infection as in this case, suggests the possibility of an etiologic agent related to the KD rather than to the EBV infection itself.     

Epstein-Barr virus infection and its role in the expanding spectrum of human diseases

Recent advances of the various laboratory tests to detect Epstein-Barr virus (EBV) infection have clarified the causative role for a spectrum of EBV-associated diseases. They include lymphoproliferative disorders (LPD), which occur in immunologically compromised individuals, Hodgkin's disease (HD), chronic active EBV infection (CAEBV), virus-associated hemophagocytic syndrome (VAHS), certain forms of T cell lymphoma, and some gastric carcinomas, in addition to the classical EBV-associated diseases such as EBV genome-positive Burkitt's lymphoma (BL), undifferentiated nasopharyngeal carcinoma (NPC) and infectious mononucleosis (IM). This review intends to introduce the recent progress of studies on EBV infection mainly from the clinical points of view.