儿童EB病毒相关性噬血淋巴组织细胞增生症的病毒学特征

Virological Features of Epstein-Barr Virus Associated Hemophagocytic Lymphohistiocytosis in Children Cases

目的了解儿童EB病毒(Epstein-Barr virus,EBV)相关性嗜血淋巴组织细胞增生症(EBV-associated hemophagocyticlymphohistiocytosis,EBV-HLH)的血清学EB病毒抗体和病毒复制水平等病毒学特征。方法对26例嗜血淋巴组织细胞增生症(HLH)和23例原发性EBV感染所致的传染性单核细胞增多症(EBV-associated,infectious mononucleosis,EBV-IM),用荧光定量PCR检测患者血清中EBV-DNA拷贝数,同时用间接免疫荧光法检测4项EBV抗体,包括:抗EBV衣壳抗原(capsid antigen,CA)IgG(EBV-CA-IgG)抗体、抗EBV衣壳抗原IgM(EBV-CA-IgM)抗体、抗EBV早期抗原(early antigen,EA)IgG(EBV-EA-IgG)抗体、抗EBV核抗原(nuclear antigen,NA)IgG(EBV-NA-IgG)抗体。结果7例HLH患者血清中EBV-DNA检测阳性,被诊断为EBV-HLH。EBV-HLH患者血清中EBV-DNA拷贝数均值为(4.586±0.107)×107/mL。从4项EBV抗体结果分析,原发感染3例(抗EBV-NA-IgG抗体阴性),既往感染或再激活4例(抗EBV-NA-IgG抗体阳性)。7例EBV-HLH患者中有3例EBV-CA-IgM阳性。23例EBV-IM患者血清中EBV-DNA检测均阳性,拷贝数均值为(6.865±0.305)×103/mL。EBV-HLH患者血清中EBV-DNA拷贝数显著高于EBV-IM患者血清中EBV-DNA拷贝数,二者比较差异有统计学意义(P=0.000)。结论EBV-HLH可以发生在EBV感染的不同时期,EBV-HLH患者血清中EBV-DNA拷贝数显著高于IM患者,外周血中EBV-DNA荧光定量PCR检测在EBV-HLH的病因诊断中比血清学抗体检测更具价值。

Objective To analyze virological features of Epstein-Barr virus associated hemophagocytic lymphohistiocytosis in children cases. Methods The patients including 26 children with hemophagocytic lymphohistiocytosis （HLH） and 23 children with infectious mononucleosis （IM）. EBV-DNA loads in sera were detected by real-time PCR assay with a commercial kit. Four antibodies, including EBV-IgG/M anti-VCA, EBV-IgG anti-EA, EBV-IgG anti-NA, were detected in sera of HLH cases. Results Seven HLH cases with positive of EBV-DNA in sera were diagnosed as Epstein-Barr virus associated hemophagocytic lymphohistiocytosis （EBV-HLH）. The mean EBV-DNA loads in sera of patients with EBV-HLH were （4. 586 ± 0. 107）×10^7 copies/mL. Of 7 EBV-HLH, there were 3 primary EBV infections （EBV-IgG anti-NA negative） and 4 reactivated or past EBV infections （EBV-IgG anti-NA positive）. All IM cases were positive of EBV-DNA in sera and mean EBV-DNA loads were （6. 865± 0. 305）×10^3 copies/mL. There were significant differences of EBV-DNA loads in sera of patients between EBV-HLH and IM （P = 0. 000）. Conclusion EBV-HLH may occur in different stages of EBV infection. Detection of EBV-DNA in sera by real-time PCR was more practical in diagnosing EBV-HLH than antibody detection. There were significant differences of EBV- DNA loads in sera of patients between EBV-HLH and IM.