67例成人EB病毒感染临床及实验室特征分析

doi:10.16150/j.1671-2870.2020.01.015

摘要/Abstract

摘要：

目的：检测成人Epstein-Barr病毒（EB病毒）感染患者的EB病毒相关抗体及EB病毒DNA、血常规、血生化指标,对其临床症状进行分析,探讨成人EB病毒感染的临床特点。方法：收集67例成人EB病毒感染患者的临床资料及实验室检测结果,并将其按年龄分为青中年组（18~59岁,19例）和老年组（≥60岁,48例）;另收集同期的49名健康体检者,按前述年龄分为2组,分别作为年龄对照组。分析成人EB病毒感染的临床特点及不同年龄段患者间的异同。结果：67例成人EB病毒感染患者中,最常见的症状为发热（37例,55.2%）;其次为淋巴结肿大（13例,19.4%）、脾肿大（9例,13.4%）、肝脏肿大（8例,11.9%）、咽部充血（6例,9.0%）和皮疹（5例,7.5%）。EB病毒感染的青中年患者与老年患者相比较,发热（84.2%比43.8%）、咽部充血（26.3%比2.1%）、皮疹（21.1%比2.1%）、肝脏肿大（31.6%比4.2%）的临床症状明显（χ²值分别为9.012、7.057、4.612、7.295,P均<0.05）。19例青中年患者中有2例伴发恶性肿瘤性疾病;而48例老年患者中有2例（4.1%）伴发嗜血细胞淋巴组织细胞增生症,17例（34.7%）伴发恶性肿瘤性疾病,2组间的恶性肿瘤患病构成比差异有统计学意义（χ²=4.15,P=0.042）。EB病毒感染老年组的T淋巴细胞总数、CD4⁺T淋巴细胞计数、B淋巴细胞计数均低于健康老年组（t分别为4.525,5.960,2.999,P均<0.05）,而EB病毒感染青中年组的淋巴细胞亚群数与健康青中年组比较,差异无统计学意义（P>0.05）。青中年EB病毒感染患者与老年患者比较,EB病毒相关抗体表达水平及肝功能指标差异无统计学意义（P均>0.05）。结论：成人EB病毒感染患者的临床表现各异,青中年患者的急性感染症状较老年患者明显,而老年患者的细胞免疫及体液免疫功能降低,且EB病毒相关肿瘤患病者构成比高。

关键词: Epstein-Barr病毒感染, 实验室检查, 临床特征, 成人

Abstract:

Objective: To study the clinical characteristics of Epstein-Barr virus(EB virus) infection in adult patients by detecting EB virus-associated antibodies, EB virus DNA, blood routine, blood biochemistry and analyzing clinical symptoms. Methods: A total of 67 adults with EB virus infection were enrolled. Patients were divided into two age groups:young and middle-aged group (18-59 years old, 19 cases) and elderly group (60 years old and above, 48 cases), and 49 healthy subjects including 30 young and middle-aged and 19 elderly people were served as aged group controls. The clinical characteristics of EB virus infection were studied and the differences between the two age groups were compared. Results: Fever was the most common presenting symptom (37 cases, 55.2%), and followed by enlarged lymph nodes(13 cases,19.4%), splenomegaly (9 cases,13.4%), liver enlargement(8 cases, 11.9%), pharyngeal congestion (6 cases, 9.0%), and rash (5 cases, 7.5%). Fever (84.2% vs 43.8%), pharyngeal congestion (26.3% vs 2.1%), rash (21.1% vs 2.1%), liver enlargement (31.6 % vs 4.2%) in young and middle-aged patients were more common than in elderly group ( χ² values: 9.012, 7.057, 4.612, 7.295, P<0.05). Two cases in young and middle-aged group had malignant tumor diseases (10.5%), while 2 cases (4.1%) in elderly group had hematopoietic lymphohistiocytosis and 17 cases (34.7 %) had malignant tumor diseases. The constituent ratio of cases with malignant tumor diseases between the two groups was significantly different ( χ²=4.15, P=0.042). The total number of T lymphocytes, count of CD4 ⁺ T lymphocytes, and B lymphocytes in the elderly group were lower than those in the healthy control group (t=4.525, 5.960, 2.999, P all <0.05), while the number of lymphocyte subsets in the young and middle-aged group was not significantly different from that in the healthy controls(P>0.05). There were no statistical differences in liver function indices and levels of EB virus-related antibodies between young and middle-aged and elderly patients(P>0.05). Conclusions: Clinical manifestations of EB virus infection in adults are varied. The symptoms of acute infection are more common in young and middle-aged patients than in the elderly patients. The cellular immunity and humoral immunity are decreased in elderly patients, and the constituent ratio of cases with EB virus-related tumors is high.

Key words: Epstein-Barr virus infection, Laboratory tests, Clinical features, Adults

中图分类号:

R511

胡颖, 包玉洁, 白玉盘, 陆观珠, 成亚娇, 郭竹英, 许洁. 67例成人EB病毒感染临床及实验室特征分析[J]. 诊断学理论与实践, 2020, 19(1): 74-79.

HU Ying, BAO Yujie, BAI Yupan, LU Guanzhu, CHENG Yajiao, GUO Zhuying, XU Jie. Analysis of clinical and laboratory characteristics of EB virus infection in 67 adult patients[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(1): 74-79.

图/表 4

表1

表2

表3

表4

参考文献 31

[1]	Sarwari NM, Khoury JD, Hernandez CM. Chronic Epstein Barr virus infection leading to classical Hodgkin lymphoma[J]. BMC Hematol, 2016, 16:19. doi: 10.1186/s12878-016-0059-3 pmid: 27437106
[2]	Landais E, Saulquin X, Houssaint E. The human T cell immune response to Epstein-Barr virus[J]. Int J Dev Biol, 2005, 49(2-3):285-292. pmid: 15906243
[3]	de Paschale M, Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions[J]. World J Virol, 2012, 1(1):31-43. doi: 10.5501/wjv.v1.i1.31 pmid: 24175209
[4]	Vedham V, Verma M, Mahabir S. Early-life exposures to infectious agents and later cancer development[J]. Cancer Med, 2015, 4(12):1908-1922. doi: 10.1002/cam4.538 URL
[5]	Cohen JI. Epstein-barr virus vaccines[J]. Clin Transl Immunology, 2015, 4(1):e32. doi: 10.1038/cti.2014.27 URL
[6]	Vine LJ, Shepherd K, Hunter JG, et al. Characteristics of Epstein-Barr virus hepatitis among patients with jaundice or acute hepatitis[J]. Aliment Pharmacol Ther, 2012, 36(1):16-21. doi: 10.1111/j.1365-2036.2012.05122.x URL
[7]	孙佳, 赵龙凤. 47例成人EB病毒感染临床分析[J]. 中华传染病杂志, 2018, 36(6):358-360.
[8]	强春倩, 荆国红, 徐学彩, 等. 104例EB病毒感染肝功能损害患者的临床特点及预后分析[J]. 中华实验和临床感染病杂志:电子版, 2014. 8(3):410-413.
[9]	宋培新, 孙静, 唐勤. 53例成人EB病毒感染相关疾病临床分析[J]. 中国血液流变学杂志, 2008, 18(4):551-554.
[10]	人类年龄划分又有新标准[J]. 民俗研究, 2001, 17(3):26.
[11]	Hislop AD, Taylor GS, Sauce D, et al. Cellular responses to viral infection in humans: lessons from Epstein-Barr virus[J]. Annu Rev Immunol, 2007, 25:587-617. doi: 10.1146/annurev.immunol.25.022106.141553 URL
[12]	Tsurumi T, Fujita M, Kudoh A. Latent and lytic Epstein-Barr virus replication strategies[J]. Rev Med Virol, 2005, 15(1):3-15. doi: 10.1002/rmv.441 URL
[13]	汪洋. EB病毒的流行病学研究进展[J]. 国际检验医学杂志, 2010, 31(12):1405-1407.
[14]	Fugl A, Andersen CL. Epstein-Barr virus and its associa-tion with disease-a review of relevance to general practice[J]. BMC Fam Pract, 2019, 20(1):62. doi: 10.1186/s12875-019-0954-3 pmid: 31088382
[15]	Kimura H, Fujiwara S. Overview of EBV-associated T/NK-cell lymphoproliferative diseases[J]. Front Pediatr, 2019, 6:417. doi: 10.3389/fped.2018.00417 URL
[16]	Vranic S, Cyprian FS, Akhtar S, et al. The role of Epstein-Barr virus in cervical cancer: A brief update[J]. Front Oncol, 2018, 8:113. doi: 10.3389/fonc.2018.00113 pmid: 29719817
[17]	Bedri S, Sultan AA, Alkhalaf M, et al. Epstein-Barr virus (EBV) status in colorectal cancer: a mini review[J]. Hum Vaccin Immunother, 2019: 15(3):603-610. doi: 10.1080/21645515.2018.1543525 URL
[18]	苗彦, 林棱, 姚瑾, 等. 60例成人 EB 病毒感染临床特点分析[J]. 中国临床医生杂志, 2015, 43(10):37-40.
[19]	Chatterjee B, Deng Y, Holler A, et al. CD8⁺ T cells retain protective functions despite sustained inhibitory receptor expression during Epstein-Barr virus infection in vivo[J]. PLoS Pathog, 2019, 15(5):e1007748. doi: 10.1371/journal.ppat.1007748 URL
[20]	Vallejo AN. CD 28 extinction in human T cells: altered functions and the program of T-cell senescence[J]. Immunol Rev, 2005, 205:158-169. pmid: 15882352
[21]	Weinberger B, Welzl K, Herndler-Brandstetter D, et al. CD28(-)CD8(+) T cells do not contain unique clonotypes and are therefore dispensable[J]. Immunol Lett, 2009, 127(1):27-32. doi: 10.1016/j.imlet.2009.08.008 pmid: 19715728
[22]	Yin H, Qu J, Peng Q, et al. Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis[J]. Med Microbiol Immunol, 2019, 208(5):573-583. doi: 10.1007/s00430-018-0570-1 URL
[23]	徐婷娟, 沈国栋, 程民, 等. T淋巴细胞亚群检测在老年肿瘤患者中的临床意义[J]. 中国临床保健杂志, 2018, 21(5):623-625.
[24]	Qin L, Jing X, Qiu Z, et al. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults[J]. Aging (Albany NY), 2016, 8(5):848-859.
[25]	Ebell MH. Epstein-Barr virus infectious mononucleosis[J]. Am Fam Physician, 2004, 70(7):1279-1287. pmid: 15508538
[26]	汪国蓉, 王强, 凡翟明, 等. 化学发光免疫分析法在检测儿童EB病毒感染中的应用[J]. 中华医院感染学杂志, 2012, 22(15):3430-3432.
[27]	Gulley ML, Tang W. Laboratory assays for Epstein-Barr virus-related disease[J]. J Mol Diagn, 2008, 10(4):279-292. doi: 10.2353/jmoldx.2008.080023 URL
[28]	Wang Z, Lv Z, Ding H, et al. Role of serum EBV-VCA IgG detection in assessing gastric cancer risk and prognosis in Northern Chinese population[J]. Cancer Med, 2018, 7(11):5760-5774. doi: 10.1002/cam4.1792 URL
[29]	Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer[J]. N Engl J Med, 2018, 378(10):973. doi: 10.1056/NEJMx180004 URL
[30]	Kim KY, Le QT, Yom SS, et al. Clinical utility of Epstein-Barr virus DNA testing in the treatment of nasopharyngeal carcinoma patients[J]. Int J Radiat Oncol Biol Phys, 2017, 98(5):996-1001. doi: 10.1016/j.ijrobp.2017.03.018 URL
[31]	Brussel A, Brack K, Muth E, et al. Use of a new RNA next generation sequencing approach for the specific detection of virus infection in cells[J]. Biologicals, 2019, 59:29-36. doi: S1045-1056(19)30026-0 pmid: 30992161

观察指标	青中年组（n=19）	老年组（n=48）	统计值	P值
白细胞计数（×10⁹/L）	7.2±3.2	7.0±4.3	t=0.027	0.979
中性粒细胞计数（×10⁹/L）	4.5±2.5	5.3±4.0	t=-0.894	0.979
单核细胞计数（×10⁹/L）	0.6±0.3	0.5±0.3	t=0.861	0.374
血小板计数（×10⁹/L）	218.2±105.6	158.3±94.5	t=2.170	0.034
ALT （U/L）	53.0(250.0,1 380.5)	26.0(15.3,90.8)	Z=-1.280	0.200
AST （U/L）	57.0(22.0,110.0)	36.5(21.5,90.8)	Z=-0.912	0.362
GGT （U/L）	84.0(23.0,151.0)	53.0(22.0,134.0)	Z=-0.710	0.478
ALP （U/L）	100(76.0,120.0)	103(70.0,150.0)	Z=-0.042	0.967
TBIL （μmol/L）	14.0(10.0,57.9)	12.6(10.2,27.4)	Z=-0.250	0.802
DBIL （μmol/L）	3.1(2.2,17.7)	2.2(2.3,7.7)	Z=-0.278	0.781
IBIL （μmol/L）	10.3(7.4,24.4)	99.0(7.2,20.1)	Z=-0.529	0.597

观察指标	EB病毒感染老年组（n=48）	健康老年组（n=19）	t值	P值
T淋巴细胞总数绝对值	1 035.8±736.9	1 519.5±1 025.2	-2.127	0.037
CD4⁺T淋巴细胞数绝对值	559.1±418.0	878.9±595.1	-2.441	0.018
CD8⁺T淋巴细胞数绝对值	462.0±470.7	582.6±471.6	-0.934	0.354
NK细胞数绝对值	309.7±345.6	434.0±323.2	-1.335	0.187
B淋巴细胞数绝对值	162.0±153.7	241.5±176.0	-2.107	0.039

观察指标	EB病毒感染青中年组（n=19）	健康青中年组（n=30）	统计值t	P值
T淋巴细胞总数绝对值	2 050.3±1592.6	1 897.5±1 195.4	0.149	0.701
CD4⁺T淋巴细胞数绝对值	1 090.4±883.8	993.6±575.2	0.202	0.655
CD8⁺T淋巴细胞数绝对值	849.4±728.5	794.8±813.5	0.050	0.823
NK细胞数绝对值	412.3±310.0	302.0±185.3	2.290	0.137
B淋巴细胞数绝对值	383.6±207.6	311.2±235.1	1.070	0.307

观察指标	青中年组	老年组	χ²值	P值
EB病毒VCA阳性	4（25.0%）	12(41.4%)	0.104	0.747
EB病毒VCA抗体IgA阳性	2(14.3%)	10（32.3%）	0.394	0.530
EB病毒VCA抗体IgG阳性	1（6.7%）	2（5.1%）	0.043	0.835
EB病毒DNA阳性	13（68.4%）	30（61.2%）	0.305	0.786