12个月以下血小板减少症患儿感染巨细胞病毒的基因型特征分析与临床意义

刘慧; 桑旭; 王磊; 周瑞; 董淮富

doi:10.16766/j.cnki.issn.1674-4152.003075

12个月以下血小板减少症患儿感染巨细胞病毒的基因型特征分析与临床意义

doi: 10.16766/j.cnki.issn.1674-4152.003075

刘慧^{1, 2},
桑旭¹,
王磊¹,
周瑞¹,
董淮富^1, ,

1.
蚌埠医学院第一附属医院儿科，安徽蚌埠 232004
2.
淮南市妇幼保健院儿内科，安徽淮南 232000

基金项目:

蚌埠医学院自然科学基金面上项目 BYKY18117

安徽高校自然科学研究重点项目 KJ2021A0742

详细信息

通讯作者:
董淮富，E-mail：987105312@qq.com

中图分类号: R373.11 R725
计量
- 文章访问数: 161
- HTML全文浏览量: 52
- PDF下载量: 11
- 被引次数: 0
出版历程
- 收稿日期: 2022-07-16
- 网络出版日期: 2023-08-28

Genotypic characteristics and clinical significance of cytomegalovirus infection in children with thrombocytopenia under 12 months old

LIU Hui^{1, 2},
SANG Xu¹,
WANG Lei¹,
ZHOU Rui¹,
DONG Huaifu^{1
, ,}

1.
Department of Pediatrics, the First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 232004, China

摘要

摘要: 目的收集婴幼儿巨细胞病毒(CMV)相关血小板减少症病例，研究糖蛋白B、H(gB、gH)基因型与CMV相关血小板减少症之间的关系。方法选取2017年1月—2021年12月在蚌埠医学院第一附属医院治疗的CMV阳性共697例，其中血小板减低的患儿(年龄＜1岁)29例，患儿均为新发初诊患儿，无持续血小板减少＞3个月。采用巢式聚合酶链反应(nPCR)和限制性长度多态性(RFLP)对gB和gH进行基因型分析。结果 697例CMV感染患儿中，先天性感染76例，围产期感染378例，产后感染243例。其中，29例患儿被诊断为血小板减少症，发生率为4.16%。29例免疫功能良好的CMV感染伴血小板减少患儿，包括7例(9.2%)先天性感染，14例(3.7%)围产期感染和8例(3.3%)产后感染。诊断时血小板计数 < 20×10⁹/L是围产期感染CMV相关血小板减少的常见表现。其中，在先天性和围产期感染组中肝胆症状的发生率显著升高。24例使用免疫球蛋白，9例使用抗病毒药物。本研究中最普遍的CMV基因型为gB1(60.7%)和gH2(57.1%)。结论血小板减少症是先天性CMV感染的常见表现，gB1基因型的毒力较强，gH2基因型与血小板减少症关系密切。
- 巨细胞病毒 /
- 血小板减少症 /
- 糖蛋白B /
- 糖蛋白H
Abstract: Objective To collect clinical cases of cytomegalovirus (CMV) related thrombocytopenia in infants and study the relationship between glycoprotein B, H (gB, gH) genotypes and CMV related thrombocytopenia. Methods A total of 697 CMV-positive cases treated at the First Affiliated Hospital of Bengbu Medical College from January 2017 to December 2021 were selected, including 29 children with hypoplastic platelets (age < 1 year), all of whom were newly first diagnosed children without persistent thrombocytopenia for >3 months. The genotypes of gB and gH were analyzed by nested polymerase chain reaction (nPCR) and restriction length polymorphism (RFLP). Results Among 697 children with CMV infection, 76 cases were congenital infection, 378 cases were perinatal infection and 243 cases were postpartum infection. Twenty-nine CMV-patients with good immune function were analyzed for related thrombocytopenia, including 7 (9.2%) congenital infection, 14 (3.7%) perinatal infection and 8 (3.3%) postpartum infection. Platelet count at diagnosis < 20×10⁹/L was a common manifestation of CMV-related thrombocytopenia in perinatal infection. Among them, the incidence of hepatobiliary symptoms found in the congenital and perinatal infection groups was significantly higher. Immunoglobulin was used in 24 cases, and antiviral drugs were used in 9 cases. The most common CMV genotypes in this study were gB1 (60.7%) and gH2 (57.1%). Conclusion Thrombocytopenia is a common clinical manifestation of congenital CMV infection. The gB1 genotype has strong virulence. The gH2 genotype is closely related to thrombocytopenia.
- Cytomegalovirus /
- Thrombocytopenia /
- Glycoprotein B /
- Glycoprotein H

HTML全文

表 1 29例年龄＜12个月的CMV患儿的基本特征

Table 1. Basic characteristics of 29 CMV children aged < 12 months

项目	先天性感染组(n=7)	围产期感染组(n=14)	产后感染组(n=8)	统计量	P值
性别(男/女，例)	4/3	8/6	5/3		1.000^c
胎龄[M(P₂₅, P₇₅)，周]	39(35, 41)	38(34, 40)	40(38, 41)	0.518^a	0.492
出生体重(x±s，g)	2 614.29±465.22	3 033.57±456.08	3 562.50±363.27	28.961^b	＜0.001
诊断时的血小板计数[M(P₂₅, P₇₅)，×10⁹/L]	29(21, 64)	21(8, 51)	23(11, 32)	3.979^a	0.025
出血[例(%)]	2(28.6)	0	1(12.5)		0.071^c
贫血[例(%)]	3(42.9)	2(14.3)	0		0.081^c
中性粒细胞减少[例(%)]	1(14.3)	4(28.6)	2(25.0)		0.863^c
呼吸系统症状[例(%)]	3(42.9)	6(42.9)	2(25.0)		0.785^c
肝胆症状[例(%)]	4(57.1)	10(71.4)	1(12.5)		0.028^c
淋巴细胞比例增加[例(%)]	5(71.4)	11(78.6)	7(87.5)		0.850^c
非典型淋巴细胞[例(%)]	3(42.9)	9(64.3)	3(37.5)		0.449^c
住院时间[M(P₂₅, P₇₅)，d]	14(10，30)	9(4，28)	8(6，10)	2.056^a	0.027^c
临床病程(复发/不复发，例)	2/5	1/13	0/8		0.205^c
CMV疾病的严重程度(中重度/轻度，例)	6/1	11/3	1/7		0.004^c
注：^a为H值，^b为F值，^c为采用Fisher精确检验。

下载: 导出CSV

表 2 各组糖蛋白B基因型分布[例(%)]

Table 2. Distribution of glycoprotein B genotypes in each group [cases (%)]

组别	中重度CMV感染				轻度CMV感染				P值^a
组别	gB1	gB2	gB3	gB1+gB3	gB1	gB2	gB3	gB1+gB3	P值^a
先天性感染	3(60.0)	1(20.0)	1(20.0)	0	1(100.0)	0	0	0	1.000
围产期感染	9(81.8)	0	2(18.2)	0	1(33.3)	1(33.3)	1(33.3)	0	0.176
出生后感染	1(100.0)	0	0	0	2(28.6)	3(42.9)	1(14.3)	1(14.3)	1.000
合计	13(76.5)	1(5.9)	3(17.6)	0	4(36.4)	4(36.4)	2(18.2)	1(9.1)	0.061
注：^a为采用Fisher精确检验。

下载: 导出CSV

表 3 CMV糖蛋白B基因型在不同类型CMV阳性患儿中的分布[例(%)]

Table 3. Distribution of CMV glycoprotein B genotypes in different types of CMV-positive children [cases (%)]

临床类型	gB基因型						合计	P值^a
临床类型	gB1	gB2	gB3	gB1+gB2	gB1+gB3	gB2+gB3	合计	P值^a
CMV相关血小板减少症	17(60.7)	5(17.9)	5(17.9)	0	1(3.6)	0	28
CMV感染	97(51.9)	39(20.9)	34(18.2)	1(0.5)	16(8.6)	0	187	0.884
CMV感染合并肝功能损害	22(68.8)	3(9.4)	4(12.5)	2(6.2)	1(3.1)	0	32	0.662
CMV感染合并呼吸系统症状	5(33.3)	4(26.7)	4(26.7)	1(6.7)	0	1(6.7)	15	0.232
CMV感染合并粒细胞减少	15(88.2)	0	1(5.9)	1(5.9)	0	0	17	0.070
注：^a为与CMV相关血小板减少症患儿比较，采用Fisher精确检验。

下载: 导出CSV

表 4 各组糖蛋白H基因型分布[例(%)]

Table 4. Distribution of glycoprotein H genotypes in each group [cases (%)]

组别	中重度CMV感染				轻度CMV感染				P值^a
组别	gH1	gH2	gH1+gH2	合计	gH1	gH2	gH1+gH2	合计	P值^a
先天性感染	4(80.0)	1(20.0)	0	5	0	1(100.0)	0	1	0.333
围产期感染	4(36.4)	6(54.5)	1(9.1)	11	0	3(100.0)	0	3	0.604
出生后感染	0	1(100.0)	0	1	3(42.9)	4(57.1)	0	7	1.000
合计	8(47.1)	8(47.1)	1(5.9)	17	3(27.3)	8(72.7)	0	11	0.529
注：^a为采用Fisher精确检验。

下载: 导出CSV

表 5 患儿CMV糖蛋白H基因型在不同类型CMV阳性患儿中的分布[例(%)]

Table 5. Distribution of CMV glycoprotein H genotypes in differenttypes of CMV positive children[cases (%)]

临床类型	gH基因型			合计	P值
临床类型	gH1	gH2	gH1+gH2	合计	P值
CMV相关血小板减少症	11(39.3)	16(57.1)	1(3.6)	28
CMV感染	360(51.6)	278(40.0)	59(8.5)	697	0.224^a
CMV感染合并肝功能损害	275(65.0)	122(28.8)	26(6.1)	423	0.010^a
CMV感染合并呼吸系统症状	182(59.3)	96(31.3)	29(9.4)	307	0.023^a
CMV感染合并粒细胞减少	1(14.3)	6(85.7)	0	7	0.502^a
注：^a为与CMV相关血小板减少症患儿比较，采用Fisher精确检验。

下载: 导出CSV

参考文献(17)

[1]	PHASUK N, KEATKLA J, RATTANASIRI S, et al. Monitoring of cytomegalovirus infection in non-transplant pediatric acute lymphoblastic leukemia patients during chemotherapy[J]. Medicine(Baltimore), 2019, 98(4): e14256. DOI: 10.1097/MD.0000000000014256.
[2]	YADAV S K, SAIGAL S, CHOUDHARY N S, et al. Cytomegalovirus infection in liver transplant recipients: current approach to diagnosis and management[J]. J Clin Exp Hepatol, 2017, 7(2): 144-151. doi: 10.1016/j.jceh.2017.05.011
[3]	STYCZYNSKI J. Who is the patient at risk of CMV recurrence: a review of the current scientific evidence with a focus on hematopoietic cell transplantation[J]. Infect Dis Ther, 2018;7(1): 1-16. doi: 10.1007/s40121-017-0180-z
[4]	GRIFFITHS P, REEVES M. Pathogenesis of human cytomegalovirus in the immunocompromised host[J]. Nat Rev Microbiol, 2021, 19(12): 759-773. doi: 10.1038/s41579-021-00582-z
[5]	JIN M J, KIM Y, CHOI E M, et al. Clinical characteristics and treatment courses for cytomegalovirus-associated thrombocytopenia in immunocompetent children after neonatal period[J]. Blood Res, 2018, 53(2): 110-116. doi: 10.5045/br.2018.53.2.110
[6]	KOTTON C N, KUMAR D, CALIENDO A M, et al. The third international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation[J]. Transplantation, 2018, 102(6): 900-931. doi: 10.1097/TP.0000000000002191
[7]	LJUNGMAN P, CAMARA R, ROBIN C, et al. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7)[J]. Lancet Infect Dis, 2019, 19(8): e260-e272. doi: 10.1016/S1473-3099(19)30107-0
[8]	MEESING A, RAZONABLE R R. New developments in the management of cytomegalovirus infection after transplantation[J]. Drugs, 2018, 78(11): 1085-1103. doi: 10.1007/s40265-018-0943-1
[9]	BARRADO L, PRIETO C, HERNANDO S, et al. Detection of glycoproteins B and H genotypes to predict the development of Cytomegalovirus disease in solid organ transplant recipients[J]. J Clin Virol, 2018, 109(12): 50-56.
[10]	GIMENO C, SOLANO C, LATORRE J C, et al. Quantification of DNA in plasma by an automated real-time PCR assay (cytomegalovirus PCR kit) for surveillance of active cytomegalovirus infection and guidance of preemptive therapy for allogeneic hematopoietic stem cell transplant recipients[J]. J Clin Microbiol, 2018, 46(10): 3311-3318.
[11]	LOGESWARAN D, LI Y, AKHTER K, et al. Biogenesis of telomerase RNA from a protein-coding mRNA precursor[J]. Proc Natl Acad Sci U S A, 2022, 119(41): e2204636119. DOI: 10.1073/pnas.2204636119.
[12]	KITAGAWA K, OKADA H, MIYAZAKI S, et al. Cytomegalovirus reactivation in esophageal cancer patients receiving chemoradiotherapy: a retrospective analysis[J]. Cancer Med, 2021, 21(10): 7525-7533.
[13]	朱艳, 周灵玲, 蓝俊伟, 等. 人巨细胞病毒DNA检测在小儿人巨细胞病毒感染诊断中的应用[J]. 中华全科医学, 2020, 18(3): 460-462, 466. doi: 10.16766/j.cnki.issn.1674-4152.001273 ZHU Y, ZHOU L L, LAN J W, et al. Application of human cytomegalovirus DNA detection in diagnosis of human cytomegalovirus infection in children[J]. Chinese Journal of General Practice, 2020, 18(3): 460-462, 466. doi: 10.16766/j.cnki.issn.1674-4152.001273
[14]	PUTRI N D, WIYATNO A, DHENNI R, et al. Birth prevalence and characteristics of congenital cytomegalovirus infection in an urban birth cohort, Jakarta, Indonesia[J]. Int J Infect Dis, 2019, 86(9): 31-39.
[15]	LEBEDEVA A, MARYUKHNICH E, GRIVEL J C, et al. Productive cytomegalovirus infection is associated with impaired endothelial function in ST-elevation myocardial infarction[J]. Am J Med, 2020, 133(1): 133-142. doi: 10.1016/j.amjmed.2019.06.021
[16]	GALITSKA G, BIOLATTI M, DE ANDREA M, et al. Biological relevance of cytomegalovirus genetic variability in congenitally and postnatally infected children[J]. J Clin Virol, 2018, 108(11): 132-140.
[17]	陈露燕, 李伟, 徐佳露, 等. 先天性巨细胞病毒感染gH基因分型与临床特征的关系[J]. 中华儿科杂志, 2019, 57(8): 597-602. CHEN L Y, LI W, XU J L, et al. Relationship between gH genotyping and clinical characteristics of children with congenital cytomegalovirus infection[J]. Chinese Journal of Pediatrics, 2019, 57(8): 597-602.