Genotypic characteristics and clinical significance of cytomegalovirus infection in children with thrombocytopenia under 12 months old
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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。 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. -
Key words:
- Cytomegalovirus /
- Thrombocytopenia /
- Glycoprotein B /
- Glycoprotein H
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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 1.000c 胎龄[M(P25, P75),周] 39(35, 41) 38(34, 40) 40(38, 41) 0.518a 0.492 出生体重(x±s,g) 2 614.29±465.22 3 033.57±456.08 3 562.50±363.27 28.961b <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) 3.979a 0.025 出血[例(%)] 2(28.6) 0 1(12.5) 0.071c 贫血[例(%)] 3(42.9) 2(14.3) 0 0.081c 中性粒细胞减少[例(%)] 1(14.3) 4(28.6) 2(25.0) 0.863c 呼吸系统症状[例(%)] 3(42.9) 6(42.9) 2(25.0) 0.785c 肝胆症状[例(%)] 4(57.1) 10(71.4) 1(12.5) 0.028c 淋巴细胞比例增加[例(%)] 5(71.4) 11(78.6) 7(87.5) 0.850c 非典型淋巴细胞[例(%)] 3(42.9) 9(64.3) 3(37.5) 0.449c 住院时间[M(P25, P75),d] 14(10,30) 9(4,28) 8(6,10) 2.056a 0.027c 临床病程(复发/不复发,例) 2/5 1/13 0/8 0.205c CMV疾病的严重程度(中重度/轻度,例) 6/1 11/3 1/7 0.004c 注:a为H值,b为F值,c为采用Fisher精确检验。 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 gB1 gB2 gB3 gB1+gB3 gB1 gB2 gB3 gB1+gB3 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。 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 gB1 gB2 gB3 gB1+gB2 gB1+gB3 gB2+gB3 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。 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 gH1 gH2 gH1+gH2 合计 gH1 gH2 gH1+gH2 合计 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。 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 gH1 gH2 gH1+gH2 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 0.224a CMV感染合并肝功能损害 275(65.0) 122(28.8) 26(6.1) 423 0.010a CMV感染合并呼吸系统症状 182(59.3) 96(31.3) 29(9.4) 307 0.023a CMV感染合并粒细胞减少 1(14.3) 6(85.7) 0 7 0.502a 注:a为与CMV相关血小板减少症患儿比较,采用Fisher精确检验。 -
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