鼻咽癌患者外周血EBV DNA水平与癌组织细胞凋亡的相关性

目的探讨鼻咽癌患者外周血EB病毒（EBV）DNA水平与癌组织细胞凋亡的相关性。方法分别采用荧光定量PCR法、流式细胞仪检测22例鼻咽癌患者外周血中EBV DNA拷贝数及鼻咽癌组织细胞的凋亡率。结果本组患者外周血EBV DNA检出率为86．5％（19／22）、中位数为2200拷贝／μl,癌组织细胞凋亡率为33．27％±13．46％;EBV DNA阳性鼻咽癌患者癌细胞凋亡率为35．93％±12．42％,EBV DNA阴性患者为16．47％±4．83％,两者比较,P〈0．05;鼻咽癌患者外周血EBV DNA拷贝数与癌细胞凋亡率呈正相关（r=0．517,P〈0．01）。结论鼻咽癌患者外周血EBV DNA水平与肿瘤细胞凋亡之间存在相关性。     

老年高血压病患者外周血T淋巴细胞亚群及红细胞免疫功能的临床研究

为探讨老年原发性高血压（OEH）患者外周血T淋巴细胞亚群及红细胞免疫功能的临床意义，对38例OEH患者的外周血T淋巴细胞亚群及红细胞免疫功能进行测定，并与对照组比较。结果表明：OEH患者CD3＋、CD4＋、CD8＋细胞百分率均低于对照组，CD4＋／DS8＋明显高于对照组（P＜0．01），其中以CD8＋细胞数量变化尤为明显，OEH患者红细胞C3b受体花环率（RBC－C3b）明显降低，而红细胞免疫复合物花环率（RBC-ICR）明显升高（P＜0．01）；CD8＋细胞数量与RBC－C3b呈正相关（T＝0．667P＜0．05），而与RBC－ICR呈负相关（r＝0．721P＜0．05）；RBC－C3b与RBC－ICR呈负相关（r＝－0．581P＜0．05）提示：OEH患者存在免疫功能紊乱，外周血T淋巴细胞亚群与红细胞免疫功能关系密切。     

不稳定性心绞痛患者红细胞变形性改变的机理及其意义

观察13例不稳定性心绞痛（USAP）患者红细胞变形能力（ED）、红细胞膜收缩蛋白（SP）、钠泵（Na＋－K＋－ATPase）活性以及血脂的变化，并分析其相关性。结果显示，与对照组比较USAP患者红细胞变形指数（DI）、SP含量及Na＋－K＋－ATPase活性均明显降低（P＜0．001、0．01、0．01），而血脂（Ch、TG）明显升高（P＜0．01、0．05）。Ch浓度与Na＋－K＋－ATPase活性呈负相关（r＝－0．5941，P＜0．01），Na＋－K＋－ATPase活性与SP含量呈正相关（r＝0．6215，P＜0．01），DI与Na＋－K＋－ATPase活性和SP含量有正相关关系（τ＝100dyn／cm2时，r＝0．5732、0．5976，P＜0．05；τ＝200dyn／cm2时，r＝0．6781、0．6497，P＜0．01）。提示USAP患者ED减退与血脂增高以及SP含量和Na＋－K＋－ATPase活性降低有关，并且变形性减退的红细胞对动脉粥样硬化形成可能有直接作用。     

HBV相关慢加急性肝衰竭患者HBsAg水平及病毒载量与近期预后研究

目的：探讨 HBV相关慢加急性肝衰竭（ACLF）患者 HBsAg 水平、HBV DNA 定量与近期预后的关系。方法选取2009年1月至2013年1月在广州市第八人民医院收治的177例HBV相关ACLF患者,比较生存组与恶化组的HBsAg水平、HBV DNA定量的差异及与 MELD 和Child-Pugh评分的相关性。结果生存组血清 HBsAg 水平为（3．67±0．41）lg COI,高于恶化组的（3．54±0．36）lg COI（P＜0．05）,血清 HBsAg 定量与近期生存呈正相关（r＝0．259,P＝0．002）,与 MELD、Child-Pugh评分呈负相关（r＝－0．450、－0．397,均P＜0．01）;据 HBsAg 定量得出曲线下面积（AUC）为0．657,cut-off值为6261COI。HBV DNA载量生存组为（5．64±1．65）lg IU/mL,恶化组为（5．88±1．73）lg IU/mL,两组比较差异无统计学意义（P＞0．05）,且与近期生存、MELD、Child-Pugh 评分均无相关性（P＞0．05）。结论血清 HBV DNA载量与 HBV相关ACLF患者的临床预后无相关性,而血清 HBsAg 水平与其临床预后呈正相关,HBsAg 可作为临床预后判断的指标。     

肝硬化患者血清HA、Ⅳ-C、LN和门静脉压力关系的研究

目的：探讨血清透明质酸（HA）、Ⅳ型胶原（Ⅳ－C）、层粘蛋白（LN）水平和门脉压力间的关系。方法：用放射免疫（RIA）法及B超测定35例肝硬化患者血清HA、Ⅳ－C、LN水平及门脉内径（Dpv）。结果：血清HA、LN水平和Dpv呈正相关,相关系数（r）分别为0．6（P＜0．01）、0．5（P＜0．01）;血清Ⅳ－C水平和Dpv无相关,r＝0．2（P＞0．05）。结论：血清HA、LN水平可作为测定门脉压力的指标。     

高血压病患者淋巴细胞内腺苷脱氨酶与白细胞介素Ⅱ相关性的研究

采用分光光度法及双抗夹心法对24例高血压病（EH）患者的淋巴细胞内腺苷脱氨酶（LADA）活性及白细胞介素Ⅱ（IL－2）水平进行检测。并与20例正常人对照，结果表明：EH患者LADA活性、IL－2水平均低于正常人（均P＜0．01）；EH患者IL－2与血压呈负相关（r＝－0．825P＜0．05）；EH患者LADA活性与IL－2呈正相关（r＝7．991P＜0．05）。提示EH患者存在IL－2改变，IL－2与血压的形成有内在联系。说明EH患者存在免疫改变，免疫参与了EH患者病理过程，EH患者LADA活性降低可能是导致IL－2水平下降的基本原因之一。     

小儿心肌疾病抗肌球蛋白抗体和粒细胞-巨噬细胞集落刺激因子的研究

为探讨病毒性心肌炎（VMC）和扩张型心肌病（DCM）发病的自身免疫机制，采用酶联免疫吸附和放射免疫技术检测30例VMC、14例DCM患儿血浆中抗肌球蛋白抗体和粒细胞-巨噬细胞集落刺激因子（GM－CSF）。结果：VMC和DCM患儿抗肌球蛋白抗体和GM－CSF的阳性率均为54．5％（24／44），而正常对照组分别为4．0％（1／25）和8．0％（2／25）（均P＜0．01），且抗肌球蛋白抗体与GM－CSF的血浆水平有正相关性（r＝0．3583，P＜0．05）。提示：抗肌球蛋白抗体和GM－CSF均参与了VMC和DCM的发病，与心肌的自身免疫损伤过程有关。     

慢性乙型肝炎患者外周血 CD8＋T 淋巴细胞功能的变化

目的：探讨慢性乙型肝炎患者 CD8＋ T 淋巴细胞功能的变化。方法利用主要组织相容性复合物（MHC）-抗原肽四聚体标记技术检测 HBV 的特异性 CD8＋ T 淋巴细胞,并检测其细胞因子的分泌能力,分析其与病毒学指标及临床生化指标的关系。结果人类白细胞相关抗原（HLA）-A 基因型为 A02或 A24的42例患者中,有11例患者至少检出一种被四聚体识别的 HBV 特异性 CD8＋ T 淋巴细胞,白细胞介素2（IL-2）及γ（IFN-γ）干扰素的分泌能力相对于其自身的外周血总 CD8＋ T 淋巴细胞显著降低（t＝14．231、10．450,P ＜0．01）。检出抗原特异性 CD8＋ T 淋巴细胞的患者,其血清ALT 的水平较阴性患者高（t＝2．306,P ＜0．05）,而 HBV DNA 水平却相对低（t＝－4．447,P ＜0．001）。结论慢性乙型肝炎患者外周血的抗原特异性 CD8＋ T 淋巴细胞的功能存在明显的缺陷,可能与病毒抗原的持续刺激导致功能耗竭有关。     

阿糖腺苷治疗儿童 EBV 相关性传染性单核细胞增多症疗效观察

目的：探讨阿糖腺苷治疗EBV感染相关性儿童传染性单核细胞增多症的临床疗效。方法选取EBV感染所致的传染性单核细胞增多症患儿64例，随机分为观察组和对照组各32例。观察组给予阿糖腺苷治疗，对照组给予更昔洛韦治疗，比较两组用药后热退、咽峡炎好转、异型淋巴细胞＜10％时间以及颈部淋巴结长径＜0．5 cm、肝脏回缩至正常、脾脏回缩至正常所需的时间；荧光定量PCR法检测两组EBV-DNA拷贝数，以EBV-DNA＜500拷贝／L为阴性，比较两组治疗后第7天、第10天EBV-DNA阴转率，观察两组不良反应。结果观察组热退时间、咽峡炎好转时间和异型淋巴细胞＜10％所需时间短于对照组（P均＜0．05），治疗后第7天EBV-DNA阴转率明显高于对照组（P＜0．05）。结论阿糖腺苷治疗儿童EBV相关性传染性单核细胞增多症有良好疗效。     

妊娠期弓形虫感染与垂直传播

对492份孕妇妊娠各期外周血及其79份新生儿脐血进行弓形虫IgM抗体检测,对57份有异常妊娠史孕妇及其20份流产物进行弓形虫DNA检测。结果孕妇弓形虫IgM抗体阳性率为10．5％（52／492）,其新生儿脐血IgM阳性率为12．6％（10／79）,垂直传播北为16．7％（5／30）;孕妇外周血DNA阳性率为12．2％（7／57）,相应流产物阳性率为5％（1／20）,垂直传播率为14．2％（1／7）。本文中观察5例先天感染的婴儿均为孕早期垂直传播所致,孕妇中期感染者无一婴儿感染,故孕早期垂直传播危险性大,早期诊断十分重要。     

EBV et immunodépression

Epstein-Barr virus (EBV), discovered in 1964, is a double-stranded DNA virus belonging to the Herpesviridae family. EBV has a lymphoid tropism with transforming capacities using different oncogenic viral proteins. This virus has two replication cycles: a lytic cycle mainly occuring during primary infection and a latent cycle allowing viral persistence into host memory B cells. More than 90% of adults are seropositive for EBV worldwide, with a past history of asymptomatic or mild primary infection. EBV infection can sometimes cause life-threatening complications such as hemophagocytic lymphohistiocytosis, and lead to the development of lymphoproliferative disorders or cancers. Risk factors associated with these phenotypes have been recently described through the study of monogenic primary immune deficiencies with EBV susceptibility. We here review the virological and immunological aspects of EBV infection and EBV-related complications with an overview of current available treatments.     

Severe EBV hepatitis treated with valganciclovir

We describe the case of an 18-year-old immunocompetent male patient with severe hepatitis during primary Epstein–Barr virus infection, treated with oral valganciclovir. During the initial therapy with corticosteroids, the patient’s clinical condition and liver function worsened, so we decided to add oral valganciclovir for its good bio-availability and previous encouraging experiences in different clinical settings, with rapid resolution of the symptoms.     

Fulminant EBV(+) T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome

This study describes the clinicopathologic features of 5 patients who developed a fulminant Epstein-Barr virus (EBV)-positive clonal T-cell lymphoproliferative disorder (LPD) after acute EBV infection. One additional patient developed a similar disorder in the setting of long-standing chronic active EBV infection. Detailed immunophenotyping, in situ hybridization for EBV early RNA-1 (EBER1) and polymerase chain reaction (PCR) analyses for immunoglobulin (Ig) heavy chain and T-cell receptor (TCR)-gamma gene rearrangements were performed on paraffin-embedded tissue from all patients. In addition, EBV strain typing and detection of the characteristic 30-bp deletion of the latent membrane protein-1 (LMP-1) gene were performed by PCR. Controls included 8 cases of uncomplicated infectious mononucleosis (IM). Patients included 4 males and 2 females with a median age of 18 years (2-37 years). Three patients were Mexican, 2 were white, and 1 was of Asian descent. All presented with fever, hepatosplenomegaly, and pancytopenia; 5 were previously healthy, but had a clinical history of a recent viral-like upper respiratory illness (1 week to 2 months), and 1 patient had documented chronic active EBV infection for 7 years. Serologic data for EBV were incomplete but titers were either negative or only modestly elevated in 3 cases. In 1 case serology was consistent with severe chronic active EBV infection. In the remaining 2 cases serologic studies were not performed. All patients died within 7 days to 8 months of presentation with T-cell LPD. On histologic examination, the liver and spleen showed prominent sinusoidal and portal lymphoid infiltrates of CD3(+), beta F1(+), EBER1(+) T cells lacking significant cytologic atypia. Two cases were CD4(+), 2 cases were CD8(+), and 2 cases had admixed CD4(+) and CD8(+) cells without clear subset predominance. All were TIA-1(+), CD56(-). Only rare B cells were noted. Marked erythrophagocytosis was present. Molecular analysis revealed identical T-cell clones in 2 or more sites (liver, spleen, lymph node) in 5 cases. All patients carried type A EBV; 4 cases had wild-type EBV-LMP, and 2 showed the 30-bp deletion. This fulminant T-cell LPD after acute/chronic EBV infection is characterized by hepatosplenomegaly, often without significant lymphadenopathy, fever, liver failure, pancytopenia, and erythrophagocytosis indicative of a hemophagocytic syndrome. EBV serology may be misleading, with lack of elevated titers. The presence of an EBER1(+) T-cell infiltrate with scant B cells should alert one to this diagnosis. Although cytologic atypia is minimal, studies for T-cell clonality confirm the diagnosis. (Blood. 2000;96:443-451)     

Epstein-Barr virus (EBV)-carrying and -expressing T-cell lines established from severe chronic active EBV infection

Four novel Epstein-Barr virus (EBV)-carrying T-cell lines, designated SIS, AIK-T8, AIK-T4, and SKN, were established from peripheral blood lymphocytes (PBL) of patients with severe chronic active EBV infection, in the presence of interleukin-2 and 4-deoxyphorbol ester. AIK-T8 and - T4 were derived from a single patient. Cell marker and genotype analyses showed that SIS, AIK-T8, and AIK-T4 had mature T-cell phenotypes with clonally rearranged T-cell receptor (TCR) genes, whereas SKN had an immature T-cell phenotype without TCR gene rearrangement. None of the cell lines expressed B, natural killer, or myeloid antigens or had Ig gene rearrangement. All lines carried EBV genomes in a single episomal form. SIS, AIK-T8, and SKN showed the same phenotype, TCR gene configuration, and/or EBV clonotype as their source or biopsied materials; therefore, they represented EBV-infected T cells proliferating in the patients. TCR gene and EBV episomal structures similar to those of AIK-T4 were not found in its source PBL, probably due to the few parental clones in vivo. All lines expressed EBV-encoded small RNA (EBER) 1, nuclear antigen (EBNA) 1, and latent membrane protein (LMP) 1, -2A, and -2B, but not other EBNAs that could be recognized by EBV-specific immune T cells. EBV replicative antigens were rarely expressed or induced. Such EBV latency reflects the in vivo situation, in which the T cells may evade immune surveillance and be insensitive to antiherpesvirus drugs. Collectively, the data suggest that EBV can target and latently infect T cells at any stage of differentiation in vivo, thus potentially causing uncontrolled T-cell proliferation. These cell lines will facilitate further analyses of possible EBV-induced oncogenicity in T cells.     

Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection

Chronic active Epstein-Barr virus (CAEBV) infection syndrome is a heterogeneous EBV-related disorder characterized by chronic fatigue, fever, lymphadenopathy, and/or hepatosplenomegaly, associated with abnormal patterns of antibody to EBV. CAEBV can range from disabling mild/moderate forms to rapidly lethal disorders. Even patients with mild/moderate disease frequently suffer adverse effects from long-term anti-inflammatory agents and have a quality of life that progressively deteriorates. It is still unknown why these individuals are unable to produce an effective immune response to control EBV, and no effective treatment is currently available. Since ex vivo-expanded EBV-specific cytotoxic T lymphocytes (EBV-CTLs) can safely restore EBV-specific cellular immune responses in immunodeficient patients, we assessed the possibility that adoptive immunotherapy might also effectively treat CAEBV infection. Following stimulation with irradiated EBV-transformed lymphoblastoid cell lines (LCLs), EBV-CTLs were successfully generated from 8 of 8 patients with the mild/moderate form of CAEBV infection. These CTLs were predominantly CD3(+) CD8(+) cells and produced specific killing of the autologous LCLs. There were 5 patients with 1- to 12-year histories of disease who were treated with 1 to 4 injections of EBV-CTLs. Following infusion, there was resolution of fatigue and malaise, disappearance of fever, and regression of lymphadenopathy and splenomegaly. The pattern and titers of anti-EBV antibodies also normalized. No toxicity was observed. There were 4 patients who did not show any relapse of disease within 6 to 36 months follow-up; one patient had recurrence of fatigue and myalgia one year after CTL infusion. We suggest that adoptive immunotherapy with autologous EBV-CTLs may represent a safe and feasible alternative treatment for patients affected with mild/moderate CAEBV infection and that this approach should be evaluated in the more severe forms of the disease.     

Serum IgA antibodies to Epstein-Barr virus (EBV) early lytic antigens are present in primary EBV infection

Primary Epstein-Barr virus (EBV) infection is characterized by the presence of IgM antibodies to viral capsid antigen and the absence of antibodies to EB nuclear antigen. Here, using a flow cytometry-based assay, we investigated whether IgA antibodies are a marker for primary infection. Serum IgA antibodies in 15 individuals with primary EBV infection reacted with 15%-55.6% of HH514-16 Burkitt lymphoma cells expressing early lytic antigens (EAs), whereas IgA antibodies in serum samples from 15 healthy EBV-seropositive individuals reacted with 0.02%-2% of cells with EAs (P<.0001). IgA antibodies in primary infection were directed against the Bam Z Epstein-Barr replication activator (ZEBRA) (BZLF1) and diffuse EA (BMRF1) EAs. Thus, IgA antibodies to EBV EAs are produced during primary EBV infection and are likely to be stimulated as a result of lytic EBV replication in mucosal sites. Detection of IgA antibodies to EA may be developed into a diagnostic tool for primary EBV infection.     

Biological aspects of Epstein-Barr virus (EBV)-infected lymphocytes in chronic active EBV infection and associated malignancies

Most primary Epstein-Barr virus (EBV) infections are clinically inapparent, but occasionally EBV infection can cause acute infectious mononucleosis. EBV has been linked to a variety of hematologic and non-hematologic malignancies. Chronic active EBV (CAEBV) infection designates a recently identified EBV-associated syndrome characterized by a variety of serious hematological disorders, including malignant lymphoma. EBV was found to infect circulating T- and/or NK-cells in patients with CAEBV infection. These EBV-infected T- and/or NK-cells express EBNA-1, LMP-1, and LMP-2A, a type II form of EBV latency, which is also observed in nasopharyngeal carcinoma (NPC), Hodgkin's disease (HD), and peripheral T-cell lymphoma. CAEBV infections may thus represent a subset of EBV-associated T- and/or NK-cell lymphoproliferative disorders.