Epstein-Barr virus-related encephalitis in a young woman: A case report

Although infectious mononucleosis due to Epstein-Barr virus (EBV) is a common disease among young individuals, central nervous system (CNS) complications are rare. In this report, we describe a case of CNS complications caused by EBV in a previously healthy young woman. She presented to our hospital with a 9-day history of headache and sore throat, followed by the development of fever and facial edema 6 days prior to admission. On Day 2 of admission, she was confused (Glasgow Coma Scale score: 10 points) and had fever, muscle weakness in her right arm and leg, stiff neck, and roving eye movement. We detected EBV in a cerebrospinal fluid (CSF) sample using a polymerase chain reaction (PCR) test. The magnetic resonance imaging of her brain revealed dural enhancement and right parietal and temporal lobe lesions. She was treated with acyclovir and high-dose steroid therapy. She responded well to treatment, recovered without neurologic sequelae, and was discharged home on Day 12.Our experience suggests that PCR detection of EBV DNA in CSF may be useful in diagnosing EBV encephalitis and that prognosis may be associated with an area of the brain that is affected and the time from symptom onset to starting treatment.     

多次发病的传染性单核细胞增多症

传染性单核细胞增多症为EB(Epstein-Barr)病毒引起的一种急性或亚急性全身性免疫异常疾病。一次患病后,可获得持久免疫力,多次发病罕见。本文报告了一例传染性单核细胞增多症,9年内3次发病,结合文献资料复习,就本病的诊断、治疗、临床分型、复发问题以及与肿瘤的关系进行了讨论。     

Establishment and characterization of a chronic infectious mononucleosislike syndrome in common marmosets

Epstein-Barr virus (EBV) was inoculated into two species of marmosets. Successful infection was established in the majority of the animals of one species, Callithrix jacchus, as evidenced by the development of high, persistent levels of antibody against virus-specific capsid and early nonstructural proteins. Antibodies also were produced against the major membrane antigen and, in some animals, against EBV nuclear antigen (EBNA) 2 but not against EBNA 1. This is the antibody profile normally noted in individuals with chronic infectious mononucleosis (IM). EBV-induced lymphoproliferation was not seen, and EBV-specific proteins were not detected in the peripheral blood lymphocytes of infected animals. Hence, EBV infection in C. jacchus apparently does not generally include extensive B-cell involvement. However, the marmosets clearly are useful as a model for EBV primary infection and also possibly for chronic IM.     

Characterization of cytokine production in infectious mononucleosis studied at a single-cell level in tonsil and peripheral blood.

Cytokine profile and production was studied at a single-cell level in cells obtained from 14 patients with acute infectious mononucleosis (IM), with less than 7 days of symptomatic disease, by use of cytokine-specific MoAbs and indirect immunofluorescence technique. In producer cells, all the studied cytokines, except IL-1, accumulated in the Golgi system, which resulted in a characteristic morphology of the staining. Less than one in a thousand mononuclear cells obtained directly from IM blood and stained within 2 h of sampling produced IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5, IL-6, IL-10, GM-CSF, tumour necrosis factor-alpha (TNF-alpha) or TNF-beta, spontaneously. However, these cells were induced to cytokine synthesis by T cell receptor ligation in vitro using immobilized anti-CD3 MoAbs for 2-3 h restimulation under conditions which did not activate normal cells. By this approach 168 +/- 120 cells/10,000 peripheral blood mononuclear cells produced IFN-gamma as compared with 10 +/- 8 cells/10,000 non-stimulated cultured cells obtained from IM patients (P < 0.001) and 1/10,000 cells obtained from healthy controls, respectively. No induced production of IL-2, IL-3, IL-4, IL-5, IL-10, GM-CSF or TNF-beta was detected in IM cells obtained from peripheral blood by this restimulation. In contrast, a spontaneous cytokine production was evident in tonsil material obtained from four IM patients tonsilectomized because of respiratory obstruction. From this site 160 +/- 40 cells/10,000 cells produced IL-2, 40 +/- 30 cells IL-6, 30 +/- 30 cells TNF-beta and 35 +/- 25 cells IFN-gamma, respectively. No such spontaneous IL-2, IL-6, TNF-beta or IFN-gamma production was evident in control cells obtained from patients tonsilectomized because of chronic tonsil hyperplasia.     

Absence of Epstein-Barr virus-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes in infectious mononucleosis.

Cytotoxic T lymphocytes (CTL) with the CD4+ phenotype that recognize major histocompatibility complex (MHC) class II antigens are detectable very frequently in cultures of human alloreactive or virus-specific T cells. The significance of these CD4+ CTL for an immune reaction in vivo is not clear. Since Epstein-Barr virus (EBV) transformed B cells express HLA-class I and class II antigens equally well both CD8+ and CD4+ CTL should be stimulated during an acute EBV infection. We analysed the MHC specificity and the phenotype of EBV-specific CTL from patients with infectious mononucleosis (IM). When tested directly without any previous culture, T cells from patients in the acute phase of IM showed specific MHC-restricted cytotoxicity against the autologous B cell line. Addition of a HLA class I specific monoclonal antibody (MoAb) but not of a HLA class II specific MoAb resulted in a complete blocking of the lytic activity. Cell sorting revealed that the entire cytotoxic activity was present in the CD8+ fraction whereas no specific CTL were detectable in the CD4+ fraction. The absence of cytotoxicity in CD4+ cells was not due to a lack of activation of these cells since both CD8+ and CD4+ cells were activated in situ, showing spontaneous growth in interleukin-2 (IL-2) and expressing the activation marker TP103. Frequency estimation revealed that 1/300-1/600 CD8+ but only 1/2000-1/4000 CD4+ T cells gave rise to a specific CTL colony after 10 days. If CD4+ colonies were tested repeatedly for cytotoxicity we found that CD4+ CTL acquired their cytotoxicity during in vitro culture. In addition, we isolated EBV-specific CD4+ T cell clones able to lyse their stimulator cells in the presence but not in the absence of lectin, even after a long period of culture. Taken together our results show that cytotoxicity mediated by CD4+ T cells does not play a role in an anti-viral immune response.     

传染性单核细胞增多症的临床病理及EB病毒定位性研究

目的 研究传染性单核细胞增多症(IM)的临床特征、病理特点、免疫表型和EB病毒原位感染特征,以提高对IM的认识和诊断水平.方法 采用HE染色以及免疫组织化学、原位杂交技术,结合临床资料分析,对15例IM进行了临床病理、免疫表型和EB病毒感染的研究.结果 (1)IM多见于儿童和青年人(中位年龄18岁),起病急,常有发热(12例),伴浅表淋巴结肿大,多数在短期内痊愈.(2)病变以T区增生为主,斑驳状改变常见,细胞混杂,种类多样,可见B细胞分化谱(活化淋巴样母细胞、免疫母细胞、浆样细胞、浆细胞),包膜不厚,间质不多.(3)病变中以CD3阳性的小T淋巴细胞为主,部分活化的淋巴样母细胞和免疫母细胞表达CD20和CD30,信号强弱不等,散在分布.(4)所有病例都有EB病毒编码的小RNA(EBER)阳性细胞,数量多少不一(10～100个/HPF),大中小淋巴细胞均可阳性,主要分布在T区,也见于套区、初级滤泡和生发中心内.结论 进一步确认了IM是EB病毒引起的一种急性自限性淋巴组织增生性疾病.IM在临床、病理、免疫表型和EB病毒感染方面都具有特点,只有综合考虑这4方面的信息才能减少错误,做出更准确的诊断.     

T lymphocyte anergy during acute infectious mononucleosis is restricted to the clonotypic receptor activation pathway.

The transient T cell anergy associated with acute infectious mononucleosis (IM) caused by the Epstein-Barr virus has been analysed in a sample of 14 IM children. Peripheral blood mononuclear cells (PBMC) obtained from IM patients showed a significant specific impairment in their proliferative response to both phytohaemagglutinin (PHA; P less than 0.05) and to an anti-CD3 MoAb (P less than 0.001), although both responses reached normal control levels by addition of a submitogenic dose of either phorbol myristate acetate (PMA) or recombinant IL-2 (rIL-2). In contrast, activation signals delivered through other surface molecules (CD2, CD28) or other transmembrane pathways (PMA plus a calcium ionophore) elicited normal or high proliferative responses in most IM PBMC. In a group of five patients tested, the synthesis of IL-2 by IM PBMC in the presence of PMA was impaired when PHA or anti-CD3 was used as stimulus, but it reached normal levels with anti-CD2 or ionophore. Lastly, PHA failed to induce IL-2 alpha receptor (IL-2R alpha) expression in IM PBMC from four tested patients, but the presence of PMA completely corrected this defect. Taken together, these results strongly suggest that the T cell anergy associated with acute IM is due to a T cell receptor (TCR)-specific impairment in the induction of genes involved in T cell proliferation (including those coding for IL-2 and IL-2R alpha) upon membrane signalling to otherwise normal T lymphocytes, since CD2, CD28 and certain transmembrane activation pathways are uncoupled from CD3 in these particular pathological conditions (and perhaps in most in vivo situations). This and other similar experimental approaches to transient secondary immunodeficiencies may help to unravel the physiopathological role of different surface molecules in T cell activation.     

EBV感染患儿临床特征及血清免疫因子水平

目的分析124例巴尔病毒(EBV)感染患儿的临床特征和血清免疫因子水平。方法选择2016年12月-2019年12月于海南医学院第一附属医院确诊的124例EBV感染患儿为研究组,根据临床表现分为传染性单核细胞增多症(IM)组43例和单纯性EBV组81例,选择同期健康体检儿童62名为对照组。记录所有患儿入组时的年龄、性别、临床症状;荧光定量PCR反应检测外周血淋巴细胞中EBV DNA载量;检测血清白细胞介素-6(IL-6)、IL-2和肿瘤坏死因子-α(TNF-α)水平,流式细胞仪分析外周血T淋巴细胞水平;Pearson相关性分析外周血T淋巴细胞亚群与EBV DNA载量之间的相关性。结果 IM组患儿的年龄为(5.13±1.56)岁,大于单纯性EBV组(P<0.05),出现发热、咽峡炎、淋巴结肿大、脾肿大、肝肿大、眼睑水肿、鼻塞、打鼾的比例为88.37%、93.02%、93.02%、48.84%、60.47%、32.56%、55.81%和46.51%,高于单纯性EBV组(P<0.05);IM组患儿的血CD3+T、CD8+T细胞、IL-6、TNF-α为分别为(73.25±7.16)%、(40.19±4.21)%、(33.68±5.71)ng/L、(72.52±11.26)ng/L高于对照组,而CD4+T、CD4+/CD8+T细胞、IL-2分别为(34.86±3.75)%、(0.89±0.15)、(10.43±3.38)ng/L则均低于对照组(P<0.05);外周血CD3+T和CD8+T细胞水平均与病毒载量呈正相关(r=0.314,0.447,P<0.05),CD4+T和CD4+/CD8+T细胞水平与病毒载量呈负相关(r=-0.425,-0.376,P<0.05)。结论 EBV感染患儿的临床症状和细胞免疫功能与病毒载量有关,有望应用于临床评估EBV感染的病情发展。     

83例传染性单核细胞增多症的实验室检查和并发症

目的 　分析传染性单核细胞增多症 (传单 )患儿的实验室检查与并发症 ,利于减少临床漏诊与误诊。方法　回顾性分析 1 995年 1月～ 2 0 0 2年 1 2月我科收治的83例传单患儿的实验室检查特点和并发症的发生情况。结果 　异型淋巴细胞比例增高见于 89 2 %的病例 ,提示为诊断传单简便有效的筛查手段 ,其增高程度与疾病的病情无关。EBV -VCA -IgM的阳性率为 88 5%对传单诊断有重要意义。 36 9%的病例心肌酶谱升高 ;6 8 1 %的病例血沉增快 ;53 9%的病例C -反应蛋白轻度增高 ;73 5%病例发生于 7岁以下儿童 ,7月份及 9份月为发病高峰 ;并发症发生率 78 3%尤以肝脏损害最常见。其次为肺部感染。结论 　大多数传单呈良性临床经过 ,且多具有较典型的临床表现 ,本病并发症常见且多样 ,可累及多种器官。对EBV -VCA -IgM阴性而临床高度怀疑该病病例可采用EBV -PCR扩增技术协助诊断。提高对本病实验室检查特点和并发症的认识 ,有助于减少临床误诊和漏诊。     

传染性单核细胞增多症临床与病原学分析

传染性单核细胞增多症(infectious m ononucleo-sis,IM)是主要由EB病毒感染所致的全身性疾病之一,还可有多种其他病原引起,如巨细胞病毒(C M V)、鼠弓形虫(Toxoplasm a gondli)、腺病毒(A D V)、人类免疫缺陷病毒(H IV)、支原体(M P)等。现将我科收集的102例具IM表现的患儿临床特征、病原学等资料及治疗结果报告如下。1资料与方法1.1一般资料2003年2月至2004年10月,在我院住院诊断为IM的患儿102例,其中男72例,女30例,男∶女=2.4∶1;年龄最小为37d,最大12岁,～1岁组26例(25.5%),～3岁组42例(41.2%),～6岁组19例(18.6%),～12岁组15例(…