91例EB病毒相关疾病儿童血浆EB病毒DNA的检测

目的:了解EB病毒（EBV）感染患儿外周血血浆中游离EBV DNA的拷贝数,确定EBV原发感染后外周血血浆中EBV游离DNA的拷贝数与发病天数及病情轻重的关系。方法:应用荧光定量PCR方法,测定73例EBV原发感染和18例EBV相关重症疾病患儿外周血血浆中EBV游离DNA。结果:①原发EBV感染患儿外周血血浆中EBV游离DNA随发病天数呈下降趋势,发病2周后很难检测到。②EBV相关重症疾病组患儿外周血血浆中EBV游离DNA阳性率明显高于原发EBV感染组,差异有显著性(89% vs 16%, P＜0.05）。结论: 原发EBV感染后随病程天数的增加,病毒复制水平逐渐下降。血浆中EBV游离DNA检测对评价EBV相关疾病的严重程度有一定参考价值。［中国当代儿科杂志,2009,11（11）：897-900］     

EB病毒相关噬血细胞性淋巴组织细胞增生症患儿的EB病毒感染特征

目的 了解儿童EB病毒(EBV)相关噬血细胞性淋巴组织细胞增生症(EBV-HLH)患儿的EBV血清学抗体及病毒复制水平等特征.方法 对67例EBV-HLH患儿和60例原发性EBV感染所致的传染性单核细胞增多症(EBV-IM)患儿的临床资料进行分析,EBV特异性抗体和血清EBV DNA载量分别采用间接免疫荧光法和荧光定量PCR测定.结果 EBV-HLH患儿EBV特异性抗体结果:EBV-CA-IgM、EBV-CA-IgG、EBV-EA-IgG和EBV-NA-IgG的阳性率分别为28.8％、100.0％、51.5％和78.8％,EBV-VCA-IgG高亲和力为78.9％,低亲和力为12.1％;血清学抗体结果显示,71.2％的患儿为EBV再激活感染,其余为急性原发EBV感染;45.5％的EBV-HLH患儿可在血清中检测到EBV DNA,其拷贝数中位数为1.976×103 copies·L-1.EBV-IM患儿的EBV-CA-IgM、EBV-CA-IgG、EBV-EA-IgG和EBV-NA-IgG阳性率分别为100.0％、100.0％、58.3％和26.7％,EBV-VCA-IgG高亲和力为18.3％,低亲和力为81.7％,EBV DNA阳性率为10.0％,DNA拷贝数均值为8.495 copies·1-1.IM患儿均为EBV原发感染状态.结论 EBV-HLH可发生在EBV原发感染或既往EBV感染再激活时期,但多数患儿由既往EBV感染再激活所致.EBV-HLH患儿血清中EBV复制水平显著高于EBV-IM患儿.     

儿童EBV感染的非肿瘤性相关疾病

EBV是一种亲人类B细胞的疱疹病毒.EBV可引起全身各系统和器官的疾病,包括肿瘤性和非肿瘤性相关疾病[1].在儿童非肿瘤性EBV感染相关性疾病中,传染性单核细胞增多症(IM) 、慢性活动性EBV感染(CAEBV)和EBV相关噬血淋巴组织细胞增生症(EBV-HLH) 最具临床意义.IM是良性自限性疾病,而CAEBV和EBV-HLH具有潜在恶性倾向,预后不良.本文就首都医科大学附属北京儿童医院(我院)诊断的IM、CAEBV和EBV-HLH各1例典型病例进行分析,以期提高对该类疾病的认识.     

儿童EB病毒相关性传染性单核细胞增多症

EB病毒相关性传染性单核细胞增多症(EBV-IM)是EB病毒原发感染后引起的急性单核-巨噬细胞系统增生性疾病.目前此病的发病率有所升高,且重症病例增多,因此特异性细胞免疫的作用机制及新的治疗方法、疫苗的研制日益成为研究热点.     

可溶性白细胞介素-2受体检测在儿童EB病毒感染相关疾病中的应用价值

目的探讨可溶性白细胞介素(白介素)-2受体检测在儿童EB病毒(EBV)感染相关疾病鉴别诊断中的应用价值。方法将72例患儿分为IM组、IM转化EBV相关的噬血细胞淋巴组织细胞增生症(EBV-HLH)组和EBV-HLH组;采用酶联免疫吸附试验(ELISA)分别检测患儿血清可溶性白介素-2受体和EBV抗体四项(EBV壳抗原VCA-IgM、VCA-IgG和EBV早期抗原EA-IgG、EBV核抗原-1 EBNA-1-IgG),荧光实时定量PCR检测患儿血浆EBV-DNA的表达,流式细胞术分析淋巴细胞亚群(CD3,CD4,CD8,CD19,CD56)。结果 72例患儿急性期可溶性白介素-2受体水平均超过2 400 U/ml;IM转化组在急性期可溶性白介素-2受体水平仅轻度增高(4 320 U/ml),与IM组(3 310 U/ml)无明显差异,治疗后却明显增高(8 970 U/ml),并接近EBV-HLH组水平(11 230U/ml);EBV抗体四项显示IM转化组和EBV-HLH组在治疗后VCA-IgG和EA-IgG仍然持续高滴度,同时EBV核抗原-1-IgG仍持续阴性;三组急性期都有EBV-DNA拷贝数从低拷贝至高拷贝的病例,治疗后IM转化组和EBV-HLH组仍可检测到EBV-DNA(3×103~4×105copies/ml);IM转化组和EBV-HLH组CD8+细胞在治疗后仍持续较高水平[(61.32±4.63)%,(68.36±4.32)%],并同时出现NK细胞(CD56+)比例下降[(9.23±3.28)%,(10.52.±3.34)%]。结论结合EBV抗体、EBV-DNA和淋巴细胞亚群检测,可溶性白介素-2受体检查有可能成为追踪观察EBV感染相关疾病的指标之一。     

儿童EB病毒相关噬血细胞淋巴组织细胞增生症NK细胞表面受体和CD107a表达

目的:研究儿童EB病毒相关噬血细胞淋巴组织细胞增生症（EBV-HLH）NK细胞表面受体和CD107a表达,为深入了解EBV-HLH发病机制提供理论依据。方法:选取2009年8月至2011年5月于北京儿童医院确诊为EBV-HLH、未接受过化学免疫治疗的住院患儿为EBV-HLH组,选取年龄、性别与EBV-HLH组1∶1匹配的健康查体儿童为正常对照组。应用流式细胞仪检测NK细胞表面受体、穿孔素及CD107a表达。予IL-2刺激后再次测定CD107a表达情况。结果:EBV-HLH组和正常对照组各8例。①两组NK细胞表面受体NKp30、NKp46、NKG2D、DNAM-1和2B4表达阳性率差异均无统计学意义,CD56+ NK细胞穿孔素表达率和CD8＋ T细胞穿孔素表达率差异均无统计学意义。②两组在IL-2刺激前CD107a、CD107a/K562、CD107a/2B4/P815、CD107a/NKG2D/P815和CD107a/2B4/NKG2D/P815表达率差异均无统计学意义。③EBV-HLH组在IL-2刺激前后CD107a表达差异无统计学意义;正常对照组IL-2刺激前后CD107a、CD107a/K562和CD107a/NKG2D/P815表达率差异有统计学意义。结论:EBV-HLH患儿NK细胞对IL-2的反应出现异常,可能与EBV-HLH的发生有关。     

儿童EB病毒脑炎24例临床分析

目的　分析儿童EB病毒脑炎的临床特征 ,探讨其早期诊断方法及治疗手段。方法　应用酶联免疫吸附试验(ELISA)检测脑脊液及血清中EBV外壳抗原抗体 (VCA IgM ) ,对 2 4例脑脊液EBVCA IgM阳性患儿的临床特征进行分析。结果　 2 3例为急性发病 ,1例为慢性起病。发热 2 4例 (10 0 % ) ;头痛、呕吐 10例 (42 % ) ;惊厥 10例(42 % ) ;意识障碍 16例 (6 7% ) ,其中昏迷 6例 ;惊厥 10例 ,伴精神症状 2例 ;脊髓炎 2例 ,颅神经损害 3例 ;呼吸衰竭 1例 ,合并传染性单核细胞增多症 1例。脑CT/MRI检查 :15例检查者 13例异常 ;脑脊液EBVCA IgM均阳性 ,血清VCA IgM 15例阳性。经 6个月至 1年随访 ,完全康复 2 1例 ,3例遗留后遗症 :1例左下肢活动障碍 ,2例轻度的智力低下并有癫疒间 发作。结论　EBV脑炎临床表现多样 ,多为急性起病 ,少数呈慢性活动性损害。伴有传染性单核细胞增多症表现者很少见。脑脊液EBVCA IgM阳性为主要确诊依据。大多数患儿预后良好 ,少数病情严重 ,可遗留后遗症。     

EB病毒相关的淋巴增生性疾病的诊断与治疗

EB病毒(EBV)感染与多种临床疾病密切相关,特别是多种淋巴增生性疾病,临床表现多样,慢性病程或经过凶险,大部分预后不良,为临床诊断和治疗的难点。现介绍部分相关疾病的临床诊断标准和治疗。     

儿童EB病毒相关噬血淋巴组织细胞增生症26例

目的探讨儿童EB病毒相关噬血淋巴组织细胞增生综合症(EBV-HLH)的病原学特征及临床实验室特点、治疗及预后相关因素。方法收集2003年8月~2006年8月我院收治的26例EBV-HLH患儿临床及实验室资料,追踪并回顾性分析。结果本组15例患儿EBV-HLH由重症传染性单核细胞增多症(IM)快速进展所致;8例为既往感染的再激活,3例由慢性活动性EB病毒感染(CAEBV)发展而来。实验室检查:26例患儿有不同程度的外周血三系减低及凝血功能异常并伴有脂质代谢紊乱,骨髓中出现吞噬血细胞现象。治疗及转归:在26例患儿中,16例患儿死亡,总死亡率61.5%。化疗组19例死亡总死亡率47.4%,非化疗组7例死亡率100%,2组有显著性差异(P=0.023)。脏器损害大于4个部位与死亡相关(P=0.009)。在10例存活患儿中,至少9例仍存在EB病毒的活动。结论EBV-HLH病情凶险,预后差,以多脏器损害者更差。早期诊断并尽早开始化疗可以提高患儿的存活率。缓解后可继续处于CAEBV感染状态下,甚至可转化成EBV相关淋巴瘤。     

儿童传染性单核细胞增多症并发EB病毒相关性噬血细胞综合征临床危险因素分析

目的 比较传染性单核细胞增多症(infectious mononucleosis,IM)和EB病毒相关性噬血细胞综合征(EBV-associated hemophagocytic syndrome,EBV-AHS)的临床特点,分析IM患儿发生EBV-AHS的临床危险因素.方法 回顾性比较我院2000年1月至2006年4月430例IM和EBV-AHS患儿临床症状、体征和实验室检查特点,采用Logistic回归分析IM患儿发生EBV-AHS的临床危险因素.结果 (1)本组IM病例中EBV-AHS发生率为3.72%(16/430),EBV-AHS组患儿热程明显长于IM组患儿,体温峰值、肝脏和脾脏肿大程度均较IM组患儿明显,但咽峡炎发生率(37.5%)显著低于IM组(91.1%),差异均有统计学意义.(2)EBV-AHS组外周血三系均低于IM组,且变异淋巴细胞升高不明显,其比例(中位数10%)显著低于IM组(中位数18%),差异亦有统计学意义.(3)EBV-ASH组肝功能损害显著重于IM组,尤其乳酸脱氢酶(LDH)(中位数为2128.5 U/L)和天冬氨酸氨基转移酶(AST)(中位数为489 U/L)水平升高显著高于IM组,且常伴有高胆红素血症及低白蛋白血症.(4)多因素Logistic回归分析发现:热程＞10 d(OR=8.097)、LDH进行性升高＞1000 U/L(OR=7.998)、低白蛋白血症(OR=7.838)、中性粒细胞＜1.5×109/L(OR=7.587)和血小板＜100×109/L(OR=7.190)是本组IM患儿发生EBV-AHS的临床危险因素,本组EBV-AHS病死率高达50%.结论 绝大多数IM患儿呈良性自限性过程,约3.7%患儿进展为EBV-ASH.热程＞10 d、LDH＞1000U/L、低白蛋白血症、中性粒细胞＜1.5×109/L、血小板＜100 x 109/L是IM患儿发生EBV-AHS的临床危险因素,该病预后凶险,病死率高,多次骨髓检查有助于及时诊断.     

Systemic type Epstein-Barr virus-related lymphoproliferative diseases in children and young adults: challenges for pediatric hemato-oncologists and infectious disease specialists

Involvement of Epstein-Barr virus (EBV) has long been known in the development of various tumor-forming proliferating diseases, such as nasopharyngeal carcinoma in adults. However, in children and young adults more attention should be focused on systemic, severe type EBV-related diseases, such as fatal infectious mononucleosis, hemophagocytic syndrome, or chronic active EBV infection (CAEBV). These disorders show the typical clinical features of hemophagocytic lymphohistiocytosis (HLH). Although viral infectious diseases are mostly taken care of by infectious disease specialists, pediatric hemato-oncologists need to intervene in the treatment of this kind of disease because of their clonal and neoplastic disease characteristics and of their hematologically problematic, rapid, and life-threatening clinical courses.     

EB病毒抗体检测在儿童EBV感染相关疾病诊断中的应用价值

目的探讨EBV四种抗体(VCA-IgM、VCA-IgG、EA-IgG、EBNA-1-IgG)在儿童EB病毒感染相关疾病中的应用。方法采用酶联免疫吸附法(ELISA)检测78例EB病毒感染儿童血清样本的EBV四种抗体。结果(1)病例年龄2月~15岁,中位年龄3岁,<4岁53例,4~8岁16例,>8岁9例;(2)78例患儿传染性单核细胞增多症51例(65.4%),呼吸道感染7例(9.0%),另外还有原发性血小板减少性紫癜、急性再生障碍性贫血、肾炎、过敏性紫癜、肝炎及隐性感染病例。(3)VCA-IgM阳性57例,阳性率73.1%;结论EBV四种抗体能动态反应EB病毒感染后的抗体水平,其敏感性高、特异性强、检测方法简单,在EB病毒感染相关疾病诊断中很有价值,非常值得推广。     

SYSTEMIC TYPE EPSTEIN-BARR VIRUS-RELATED LYMPHOPROLIFERATIVE DISEASES IN CHILDREN AND YOUNG ADULTS: Challenges for Pediatric Hemato-Oncologists and Infectious Disease Specialists

Involvement of Epstein-Barr virus (EBV) has long been known in the development of various tumor-forming proliferating diseases, such as nasopharyngeal carcinoma in adults. However, in children and young adults more attention should be focused on systemic, severe type EBV-related diseases, such as fatal infectious mononucleosis, hemophagocytic syndrome, or chronic active EBV infection (CAEBV). These disorders show the typical clinical features of hemophagocytic lymphohistiocytosis (HLH). Although viral infectious diseases are mostly taken care of by infectious disease specialists, pediatric hemato-oncologists need to intervene in the treatment of this kind of disease because of their clonal and neoplastic disease characteristics and of their hematologically problematic, rapid, and life-threatening clinical courses.     

Clinical and laboratory results of 270 children with infectious mononucleosis北大核心CSCD

Objective To summarize the clinical and laboratory characteristics of infectious mononucleosis (I M) in children. Methods Clinical features and laboratory results of 270 cases with IM admitted to the Department of Pediatrics in Strategic Support Force Medical Center of People's Liberation Army from January 2012 to December 2020 were retrospectively analyzed. χ2 test was used for comparison between groups. Results IM mainly occurred in children aged 5 months to 18 years old in autumn and spring. The highest incidence rate (105 cases, 38.9 %) was 3 - <6 years old (preschoolers). There were 253 cases (93.7%) with fever, 266 cases (98.5 %) with adenopharyngitis, 196 cases (72.6%) with tonsil pseudomembrane or exudation, 248 cases (91.9%) with cervical lymphadenopathy, 92 cases (34.1%) with eyelid edema, 202 cases (74.8%) with nasal obstruction, 124 cases (45.9%) with nasal obstruction and snoring, 24 cases (8. 9 %) with rash, and 112 cases (41.5%) with splenomegaly. A total of 225 cases (83.3%) presented with typical triplets of IM (fever, adenopharyngitis and cervical lymphadenopathy). Sixty - two IM patients were complicated with pulmonary infections and 3 cases with diarrhea. The main co - infection pathogens in children with IM were Mycoplasma pneumonia (M P) (79 cases, 29.3%), influenza A or B virus (34 cases, 12.6%), Streptococcus pneumonia (S P) (18 cases, 6.7%), adenovirus (22 cases, 8.1%) and cytomegalovirus (3 cases, 1.11%). A total of 46 cases (17.0%) had multiple infections. Laboratory test results suggested that absolute lymphocyte count 5. 0 x 109/L was found in 199 cases (73.7%), and abnormal lymphocyte ratio > 0.10 was found in 225 cases (83.3%). Some children had elevated transaminase levels. Epstein - Barr virus capsid antigen - immunoglobulin M (EBV - VCA - IgM) was positive in 249 cases (92.2%), Epstein - Barr virus capsid antigen - immunoglobulin G (EBV - VCA - IgG) was positive in 238 cases (88.1%), and Epstein - Barr virus nuclear antigen - immunoglobulin G (EBV - NA - IgG) was negative in all cases. EBV - VCA - IgG showed low affinity in all cases (< 40%). EBV DNA tests of peripheral blood plasma were carried in 153 cases, of which 118 cases (77.1%) were positive. Conclusions EBV related IM mainly attacks preschoolers. Most patients are presented with typical triplets of IM. Eyelid edema, nasal obstruction, snoring, splenomegaly and elevated transaminase levels are prevalent in IM children. Most cases have a favorable prognosis. © 2022 ＣｈｉｎＪＡｐｐｌＣｌｉｎＰｅｄｉａｔ. All rights reserved.     

Reed-Sternberg cells in atypical primary EBV infection

The presence of Epstein-Barr virus (EBV) in the Hodgkin's/Reed-Sternberg (HRS) cells of a significant proportion of cases of Hodgkin's lymphoma (HL) is a matter of consideration when a case of presumptive HL has to be differentiated from infectious mononucleosis (IM). A 15-y-old boy was admitted with a presumptive diagnosis of extranodal HL, based on the biopsy of a painless ulcer on the right mandibular alveolar crest. Histologic examination of the lesion was consistent with mixed cellularity HL. The patient additionally presented with hepatosplenomegaly and regional lymphadenopathy. Serology for EBV was indicative of acute infection. Histological examination of regional lymphoid tissue was consistent with immunologic activation due to primary EBV infection. The patient was left untreated, under close observation. All clinical findings resolved within 3 mo and EBV viral capsid antigen (VCA) IgM antibodies converted to negative after 6 mo. A 3-y follow-up period was uneventful.     

宏基因组二代测序在伴有中枢神经系统受累儿童噬血细胞综合征中的应用价值

目的 探究宏基因组二代测序(metagenomic next-generation sequencing,mNGS)技术检测伴有中枢神经系统受累的噬血细胞综合征患儿颅内EB病毒(Epstein-Barr virus,EBV)感染的应用价值及临床意义。方法 回顾性分析30例伴有中枢神经系统受累的噬血细胞综合征患儿的脑脊液mNGS结果,与脑脊液EBV-DNA定性检测、血清EBV抗体谱检测结果进行比较,以治疗前后血清EBV-DNA拷贝数变化反映针对性治疗效果。结果 脑脊液mNGS EBV检测阳性率为100%(30/30),高于脑脊液EBV-DNA定性检测阳性率(10%,3/30;P<0.001),与血清EBV抗体谱检测阳性率(93%,28/30)比较差异无统计学意义(P>0.05)。中位mNGS EBV检出序列数为2 400,治疗前血清EBV-DNA拷贝数与EBV检出序列数呈中度正相关(rs=0.693,P<0.001)。多元线性回归分析结果显示,治疗前血清EBV-DNA拷贝数越高,脑脊液mNGS EBV检出序列数越高(P<0.05)。结论 EBV相关噬血细胞综合征容...