抗EB病毒衣壳抗原IgG抗体亲合力诊断儿童传染性单核细胞增多症的价值及患儿免疫状态的变化

Role of the avidity of Epstein-Barr virus capsid antigen-speci?c IgG antibodies and immunological changes among children with infectious mononucleosis

目的探讨抗EB病毒衣壳抗原(EBV-CA)IgG抗体亲合力对EB病毒(EBV)感染传染性单核细胞增多症(IM)的诊断价值及患儿免疫状态的变化。方法选取行抗EBV-CAIgG抗体亲合力及抗EBV-CAIgM抗体检测的儿童5882例,其中IM500例、非IM5382例,检测抗EBV-CAIgG抗体亲合力、抗EBV-CAIgM抗体、EBVDNA载量、外周血异型淋巴细胞(简称异淋)比例和外周血淋巴细胞亚群。采用受试者工作特征(ROC)曲线评价抗EBV-CAIgG抗体亲合力、抗EBV-CAIgM抗体、异淋比例和EBVDNA单项及联合检测诊断IM的效能,并观察IM患儿的免疫状态。另选取临床诊断为IM并检测EBVDNA和淋巴细胞亚群的患儿502例,探讨EBVDNA阳性及阴性IM患儿的细胞免疫状况。结果在5882例儿童中,抗EBV-CAIgG抗体亲合力、抗EBV-CAIgM抗体、EBVDNA和异淋比例4项指标任意1项阳性的患儿为1031例(17.53%),其中IM的发生率最高(38.1%)。ROC曲线分析结果显示,抗EBV-CAIgG抗体亲合力、抗EBV-CAIgM抗体、异淋比例和EBVDNA诊断IM的曲线下面积(AUC)分别为0.883、0.729、0.788和0.664,4项指标联合检测的AUC为0.847。依据年龄将1031例患儿分为婴儿组(<1岁)、幼儿组(1~3岁)、学龄前期组(4~6岁)和学龄期组(7~17岁)。除婴儿组外,其他3组中的IM患儿CD3-CD16+CD56+自然杀伤(NK)细胞比例、CD3-CD19+B细胞比例、CD3+CD4+T细胞比例及CD4+/CD8+比值显著低于非IM患儿(P<0.01),CD3+T细胞比例、CD3+CD8+T细胞比例显著高于非IM患儿(P<0.01)。婴儿组中的IM患儿CD3-CD19+B细胞比例显著低于非IM患儿(P<0.01),CD3+T细胞、CD3+CD8+T细胞比例显著高于非IM患儿(P<0.01),而CD3-CD16+CD56+自然杀伤(NK)细胞比例、CD3+CD4+T细胞比例、CD4+/CD8+比值IM患儿与非IM患儿之间差异无统计学意义(P>0.05)。EBVDNA阳性IM患儿与阴性IM患儿比较,上述变化更明显。结论抗EBV-CAIgG抗体亲合力对IM的诊断价值优于异淋比例、抗EBV-CAIgM抗体和EBVDNA。IM患儿细胞免疫功能明显紊乱,EBVDNA阳性的IM患儿紊乱程度更严重。

Objective To evaluate the role of the avidity of Epstein-Barr virus (EBV)capsid antigen(EBV-CA)-specific IgG antibodies and immunological changes among children with infectious mononucleosis (IM). Methods A total of 5 882 children (500 cases of IM and 5 382 cases of non-IM) were enrolled for determining the avidities of EBV-CA IgG antibodies and EBV-CA IgM antibodies. The avidities of EBV-CA IgG antibodies and EBV-CA IgM antibodies,EBV DNA load, heterotypic lymphocytes and lymphocyte subsets in peripheral blood were determined. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of the avidities of EBV-CA IgG antibodies and EBV-CA IgM antibodies,heterotypic lymphocyte percentage and EBV DNA individually and combinedly in the diagnosis of IM. The immunological changes among children with IM were observed. Totally,502 clinically assigned IM child samples conducted EBV DNA and lymphocyte subset determinations were reviewed as well,and the immunological changes were compared between EBV DNA positive and negative samples. Results A total of 1 031 of 5 882 (17.53%) children got any one of the 4 indicators with the avidities of EBV-CA IgG antibodies and EBV-CA IgM antibodies,heterotypic lymphocyte percentage and EBV DNA as a positive control. IM ranked top (38.1%) in the disease panel. Receiver operating characteristic (ROC) curve analysis revealed that the areas under curve (AUC) for the avidities of EBV-CA IgG antibodies and EBV-CA IgM antibodies, heterotypic lymphocyte percentage and EBV DNA reached to 0.883,0.729,0.788 and 0.664,respectively, while the 4 indicators' combined analysis got the AUC of 0.847. The 1 031 children were classified into 4 groups as infant (<1-year-old),baby (1-3-year-old),preschool age (4-6-year-old) and school age (7-17-year-old) groups. Except infant group,in the other 3 groups,IM patients had lower proportions of CD3- CD16+CD56+ natural killer(NK) cells,CD3- CD19+B cells,CD3+CD4+ T cells and CD4+/CD8+ ratio than those of non-IM patients (P<0.01),and they had higher proportions of CD3+ T cells and CD3+CD8+ T cells than those of non-IM patients (P<0.01). In infant group,IM patients had lower CD3- CD19+ B cell proportion (P<0.01) and higher CD3+ T cell,CD3+CD8+T cell proportions than non-IM patients (P<0.01). There was no statistical significance of CD3- CD16+CD56+ NK cell proportion,CD3+CD4+ T cell proportion and CD4+/CD8+ ratio between IM and non-IM patients (P>0.05). In IM patients,the alteration of lymphocyte subsets got more significance in EBV DNA positive patients than negative patients. Conclusions For the diagnosis of IM,the avidity of EBV-CA IgG antibody is more efficient than heterotypic lymphocyte percentage,EBV-CA IgM antibody and EBV DNA. Cell immune status is disturbed in IM children,and is even worse for those with positive EBV DNA.