肾病综合征患儿EB病毒和淋巴细胞亚群变化及其与病情进展的关系

Changes in Epstein-Barr virus infection and lymphocyte subsets in children with nephrotic syndrome and their associations with disease progression

摘要

目的 观察肾病综合征(NS)患儿EB病毒(EBV)和淋巴细胞亚群变化,并分析两者与病情进展的关系。方法 选取2020年8月至2022年8月安徽省儿童医院收治的NS患儿79例纳入NS组,另选取同期于本院体检的健康儿童79例纳入对照组.比较对照组、NS组EBV-脱氧核糖核酸(DNA)载量与淋巴细胞亚群变化;用Pearson相关性分析法分析NS组EBV-DNA载量与淋巴细胞亚群的相关性;根据激素敏感情况将NS患儿分为敏感组、抵抗组,根据是否复发将患儿分为未复发组、复发组、频繁复发组,比较各组EBV-DNA载量与淋巴细胞亚群变化。结果 与对照组相比,NS组EBV-DNA、EBV抗体衣壳抗原免疫球蛋白M抗体(VCA-IgM)、衣壳抗原免疫球蛋白G抗体(VCA-IgG)阳性率,以及EBV-DNA载量、CD8⁺T淋巴细胞构成比升高,CD3⁺、CD4⁺T淋巴细胞构成比及CD4⁺/CD8⁺比值降低,差异均有统计学意义(χ²/t值介于4.674~28.535之间,P<0.05);Pearson相关性分析法显示,NS组EBV-DNA载量与CD8⁺T淋巴细胞构成比表现为正相关性(r=0.595,P<0.05),与CD3⁺、CD4⁺T淋巴细胞构成比及CD4⁺/CD8⁺比值表现为负相关性(r值分别为-0.642、-0.557、-0.657,P<0.05);与敏感组比较,抵抗组EBV-DNA、抗VCA-IgM、抗VCA-IgG阳性率,以及EBV-DNA载量、CD8⁺T淋巴细胞构成比升高,CD3⁺、CD4⁺T淋巴细胞构成比及CD4⁺/CD8⁺比值降低,差异均有统计学意义(χ²/t值介于2.194~6.254之间,P<0.05);未复发组、复发组、频繁复发组的EBV-DNA、抗VCA-IgM、抗VCA-IgG阳性率,以及EBV-DNA载量、CD8⁺T淋巴细胞构成比依次升高,CD3⁺、CD4⁺T淋巴细胞构成比及CD4⁺/CD8⁺比值依次降低,差异均有统计学意义(χ²/F值介于7.595~31.882之间,P<0.05)。结论 EBV感染、淋巴细胞亚群变化与肾病综合征发生及病情进展密切相关,且两者具有显著相关性.

Abstract

Objective To investigate changes in Epstein-Barr virus (EBV) infection and lymphocyte subsets in children with nephrotic syndrome (NS), and to analyze associations of EBV load and lymphocyte subsets with disease progression. Methods A total of 79 children with NS who admitted to Anhui Provincial Children's Hospital from August 2020 to August 2022 were enrolled in NS group, and 79 age-matched healthy children who underwent physical examination in our hospital during the same period were selected as controls. The changes in EBV-deoxyribonucleic acid (DNA) load and lymphocyte subsets (CD3⁺, CD4⁺, CD4⁺T cells, and CD4⁺/CD8⁺ ratio) were compared between the two groups. Pearson correlation analysis was used to analyze association between EBV-DNA load and lymphocyte subsets in the NS group. The patients were further stratified according to steroid sensitivity (steroid-sensitive group and steroid-resistant group) and relapse status (non-relapse group, relapse group and frequent relapse group) for subgroup comparisons. Results Compared with the control group, the positive rates of EBV-DNA, EBV antibody capsid antigen immunoglobulin M antibody (VCA-IgM) and EBV capsid antigen immunoglobulin G antibody (VCA-IgG), EBV-DNA load and CD8⁺T lymphocyte constituent ratio in the NS group elevated, while CD3⁺, CD4⁺T lymphocyte constituent ratio and CD4⁺/CD8⁺ ratio descended, and the differences were statistically significant (χ²/t value ranged from 4.674 to 28.535, all P<0.05). Pearson correlation analysis showed that in the NS group EBV-DNA load was positively correlated with CD8⁺T lymphocyte constituent ratio (r=0.595, P<0.05), while negatively correlated with CD3⁺, CD4⁺T lymphocyte constituent ratios and CD4⁺/CD8⁺ ratio (r=-0.642, -0.557 and -0.657 respectively, all P<0.05). Compared with the steroid sensitive group, the positive rates of EBV-DNA, anti-VCA-IgM and anti-VCA-IgG, EBV-DNA load and CD8⁺T lymphocyte constituent ratio increased in the steroid resistant group, while the CD3⁺, CD4⁺T lymphocyte constituent ratios and CD4⁺/CD8⁺ ratio decreased, and the differences was statistically significant (χ²/t value ranged from 2.194 to 6.254, all P<0.05). The positive rates of EBV-DNA, anti-VCA-IgM and anti-VCA-IgG, EBV-DNA load and CD8⁺T lymphocyte constituent ratio increased successively in the non-relapse group, the relapse group and the frequent relapse group, while the CD3⁺, CD4⁺T lymphocyte constituent ratios and CD4⁺/CD8⁺ ratio decreased successively, and the differences were statistically significant (χ²/F value ranged from 7.595 to 31.882, all P<0.05). Conclusion EBV infection and lymphocyte subsets dysregulation are closely associated with pathogenesis and progression of NS, and there is a significant correlation between the two.

关键词

肾病综合征 / 儿童 / EB病毒 / 淋巴细胞亚群 / 复发

Key words

nephrotic syndrome / children / EB virus / lymphocyte subset / relapse

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基金资助

安徽省医科大学校科研基金项目(2022xkj243)