血清EB病毒抗体联合血清白介素-27、Toll样受体4检查在传染性单核细胞增多症诊断中的应用

doi:10.19871/j.cnki.xfcrbzz.2025.01.008

摘要/Abstract

摘要： 目的探究血清EB病毒（Epstein-Barr virus,EBV）抗体IgM/IgG（viral capsid protein-immunoglobulin M/viral capsid protein-immunoglobulin G,VCA-IgM/IgG）联合白介素-27（interleukin 27,IL-27）、Toll样受体4（Toll-like receptor 4,TLR4）检测在传染性单核细胞增多症（infectious mononucleosis,IM）诊断中的应用。方法选取武汉市第三医院在2022年3月至2024年3月期间就诊且符合研究条件的58例IM患者为研究对象（IM组）,另取同期体检健康者60例作为对照组。采用全自动化学发光仪以及配套试剂进行VCA-IgM/IgG检测。采用ELISA法检测血清中IL-27、TLR4的蛋白表达;Spearman法分析血清VCA-IgM/IgG、IL-27、TLR4水平与IM患者疾病分期的相关性;ROC曲线分析血清VCA-IgM/IgG、IL-27和TLR4水平对IM患者的诊断价值。结果 IM组的VCA-IgM/IgG阳性率显著高于对照组的阳性率（P<0.05）,血清IL-27和TLR4水平显著高于对照组（均 P<0.05）。前、中、后期患者血清VCA-IgM/IgG阳性率及IL-27、TLR4水平均呈逐渐升高趋势（均P<0.05）。血清VCA-IgM/IgG、IL-27、TLR4水平与IM患者疾病分期呈正相关（P<0.05）。VCA-IgM/IgG、IL-27、TLR4是发生IM的独立影响因素（P<0.05）。血清VCA-IgM/IgG、IL-27和TLR4单独检测IM的敏感度分别为74.14%、81.03%、68.97%,特异度分别为80.00%、86.67%、91.67%,三者联合诊断IM的敏感度为93.10%,特异度为78.33%,准确率为85.59%,与临床诊断一致性较高（Kappa值=0.713,P<0.001）。结论血清VCA-IgM/IgG阳性表达率及IL-27、TLR4水平在IM患者中均升高,三者联合对IM患者具有较高的诊断价值。

关键词: EB病毒抗体, 白介素-27, Toll样受体4, 传染性单核细胞增多症, 诊断

Abstract: Objective To explore the application of serum EB virus (EBV) antibody viral capsid protein-immunoglobulin M/viral capsid protein-immunoglobulin G(VCA-IgM/IgG) combined with interleukin-27 (IL-27) and Toll-like receptor 4 (TLR4) testing in the diagnosis of infectious mononucleosis (IM). Method From March 2022 and March 2024, 58 patients with IM who visited our hospital and met the research criteria were included as the study subjects, and 60 healthy individuals who underwent physical examinations were included as the control group. Fully automatic chemiluminescence analyzer and supporting reagents were applied for VCA-IgM/IgG detection. ELISA method was applied to detect the protein expression of IL-27 and TLR4 in serum. Spearman method was applied to analyze the correlation between serum VCA-IgM/IgG, IL-27, TLR4 levels and disease staging in IM patients. ROC curve was applied to analyze the diagnostic value of serum VCA-IgM/IgG, IL-27, and TLR4 levels in IM patients. Result The positive rate of VCA-IgM/IgG in the IM group was obviously higher than that in the control group (P<0.05), and the levels of serum IL-27 and TLR4 were obviously higher than those in the control group (P<0.05). The positive rate of serum VCA-IgM/IgG and the levels of IL-27 and TLR4 in patients in the early, middle, and late stages showed a gradually increasing trend (P<0.05). The levels of serum VCA-IgM/IgG, IL-27, and TLR4 were positively correlated with the disease staging of IM patients (P<0.05). VCA-IgM/IgG, IL-27, and TLR were independent influencing factors for the occurrence of IM (P<0.05). The sensitivity of detecting IM with serum VCA-IgM/IgG, IL-27, and TLR4 alone was 74.14%, 81.03%, and 68.97%, respectively, the specificity was 80.00%, 86.67%, and 91.67%, respectively, the sensitivity, specificity, and accuracy of the combined diagnosis for IM were 93.10%, 78.33%, and 85.59%, respectively, which were consistent with clinical diagnosis (Kappa value=0.713, P<0.001). Conclusion The positive expression rate of serum VCA-IgM/IgG and the levels of IL-27 and TLR4 are all elevated in IM patients, and the combination of the three has high diagnostic value for IM patients.

Key words: Epstein-Barr virus antibody, Interleukin-27, Toll-like receptor 4, Infectious mononucleosis, Diagnosis

中图分类号:

R512.7

刘婷, 桑娟, 高思洋, 金泉, 王丽艳, 倪文昌. 血清EB病毒抗体联合血清白介素-27、Toll样受体4检查在传染性单核细胞增多症诊断中的应用[J]. 新发传染病电子杂志, 2025, 10(1): 39-43.

Liu Ting, Sang Juan, Gao Siyang, Jin Quan, Wang Liyan, Ni Wenchang. Application of serum EB virus antibody combined with serum IL-27 and TLR4 testing in the diagnosis of infectious mononucleosis[J]. Electronic Journal of Emerging Infectious Diseases, 2025, 10(1): 39-43.

参考文献

[1] FISCHER F, MÜCKE J, WERNY L, et al. Evaluation of novel Epstein-Barr virus-derived antigen formulations for monitoring virus-specific T cells in pediatric patients with infectious mononucleosis[J].Virol J, 2024, 21(1):139.
[2] 胡可, 施逸怡, 李妞妞, 等. 青少年和成人EB病毒相关传染性单核细胞增多症抗病毒治疗的研究进展[J].中华传染病杂志, 2023, 41(7):477-482.
[3] DE PAOR M, BOLAND F, CAI X, et al.Derivation and validation of clinical prediction rules for diagnosis of infectious mononucleosis: a prospective cohort study[J].BMJ Open, 2023, 13(2):e068877.
[4] 黄博, 董艳迎, 宋琳岚. 儿童传染性单核细胞增多症348例临床特征分析[J].临床儿科杂志, 2024, 42(8):678-683.
[5] 靳丹丹. 传染性单核细胞增多症的临床和免疫分析[D].苏州:苏州大学, 2021.
[6] 肖华, 李志霞, 周君. 血清sI-2RL、IL-27及IL-36对重症急性胰腺炎并发急性肾损伤的预测价值[J].检验医学与临床, 2024, 21(11):1617-1621.
[7] GAO L, XIONG YJ, LIANG YX, et al.The effects of IL-27 and IL-35 gene variation and expression levels on the susceptibility and clinical manifestations of pulmonary tuberculosis[J].Front Immunol, 2024, 15:1267624.
[8] 蔡宏彩. PTX-3、CysC及IL-27检测对脓毒症患者病情诊断及预后价值研究[J].中国免疫学杂志, 2022, 38(24):3039-3043.
[9] 李增沛, 李靖. 变应性鼻炎患者TNF-α、Tim-1及TLR4变化与病情程度的相关性研究[J].中国耳鼻咽喉颅底外科杂志, 2023, 29(6):50-53.
[10] 叶东梅, 张志伟, 刘勇. 传染性单核细胞增多症的病理分期与鉴别诊断[J].中华病理学杂志, 2019, 48(5):421-424.
[11] 中华医学会儿科学分会感染学组, 全国儿童EB病毒感染协作组. 儿童主要非肿瘤性EB病毒感染相关疾病的诊断和治疗原则建议[J].中华儿科杂志, 2016, 54(8):563-568.
[12] 张玉凤, 何一秀, 赵少杰, 等. 传染性单核细胞增多症儿童的维生素D水平与肝功能的相关性研究[J].新医学, 2023, 54(9):655-659.
[13] PEREIRA JG, LEON LAA, DE ALMEIDA NAA, et al.Higher frequency of Human herpesvirus-6 (HHV-6) viral DNA simultaneously with low frequency of Epstein-Barr virus (EBV) viral DNA in a cohort of multiple sclerosis patients from Rio de Janeiro, Brazil[J].Mult Scler Relat Disord, 2023, 76:104747.
[14] DAMANIA B, KENNEY SC, RAAB-TRAUB N.Epstein-Barr virus: Biology and clinical disease[J].Cell, 2022, 185(20):3652-3670.
[15] 段丽敏, 尹光丽, 田甜, 等. 血浆EBV核酸载量对成人继发性噬血细胞综合征患者临床特征及预后的影响[J].中国实验血液学杂志, 2024, 32(4):1238-1247.
[16] OLADIPO EK, OJO TO, ELEGBELEYE OE, et al.Exploring the nuclear proteins, viral capsid protein, and early antigen protein using immunoinformatic and molecular modeling approaches to design a vaccine candidate against Epstein Barr virus[J].Sci Rep, 2024, 14(1):16798.
[17] 周雪, 詹雨薇, 武正菊, 等. 鼻咽癌合并EB病毒感染外周血LMP-1、p53和Ki67表达与疾病进展的相关性[J].中华医院感染学杂志, 2024, 34(2):239-242.
[18] OTTO C, RADBRUCH H, WILKEN D, et al.Frequent intrathecal production of antibodies to the viral capsid antigen of Epstein-Barr virus in patients with central nervous system post-transplant lymphoproliferative disorder[J].J Neuroimmunol, 2022, 369:577902.
[19] 操晓莉, 陈梅俐, 胡祥松, 等. VCA-IgM与EB-DNA对儿童传染性单核细胞增多症的诊断效能[J].中华医院感染学杂志, 2023, 33(11):1741-1745.
[20] 曾江辉, 兰会华, 朱旭, 等. 血清c-Myc与EB病毒抗体联合检测对鼻咽癌的诊断价值[J].广西医科大学学报, 2017, 34(11):1564-1567.
[21] 唐方平, 刘义强, 李娜, 等. 慢性肾脏病患者血清IL-27、VASH-1水平与疾病进展的关系及其诊断价值[J].中国中西医结合肾病杂志, 2024, 25(5):412-416.
[22] CIECKO AE, SCHAUDER DM, FODA B, et al.Self-Renewing Islet TCF1+ CD8+ T Cells Undergo IL-27-Controlled Differentiation to Become TCF1- Terminal Effectors during the Progression of Type 1 Diabetes[J].J Immunol, 2021, 207(8):1990-2004.
[23] ZELAZOWSKA-RUTKOWSKA B, NIEWINSKA G, TOCZYLOWSKI K, et al.Comparison of the interleukin 27 expression for the acute and chronic phase of mononucleosis in children[J].Cytokine, 2021, 141:155395.
[24] 张姗姗. 不同吸入氧浓度对AECOPD合并Ⅱ型呼吸衰竭无创机械通气患者血气指标及血清HMGB1、IL-27水平的影响[J].实用临床医学, 2023, 24(6):15-18,23.
[25] 张润春, 李树华, 王玉珍, 等. 血清TLR4、TIMP-1水平与小儿热性惊厥临床特征的关系及对继发癫痫的预测价值[J].检验医学与临床, 2024, 21(14):2089-2093.
[26] MUSCAT SM, BUTLER MJ, BETTES MN, et al.Post-operative cognitive dysfunction is exacerbated by high-fat diet via TLR4 and prevented by dietary DHA supplementation[J].Brain Behav Immun, 2024,116:385-401.
[27] 蔡东峰, 杨子肖, 钟超, 等. miR-515-5p靶向Toll样受体4调控髓样分化因子88/NF-κB通路抑制骨关节炎软骨细胞凋亡及炎症反应的分子机制研究[J].中国修复重建外科杂志, 2024, 38(3):315-323.
[28] KANAI K, KAGEYAMA S, YOSHIE O.Involvement of TLR4 in Acute Hepatitis Associated with Airway Infection of Murine γ-Herpesvirus 68[J].J Immunol, 2023, 211(10):1550-1560.