| 摘要: |
| ［摘要］ 目的 探讨EB病毒（EBV）感染与结缔组织病相关间质性肺疾病（CTD-ILD）严重程度及免疫失衡的关联性。方法 回顾性分析2023年9月至2025年1月湖北文理学院附属襄阳市中心医院收治的63例CTD-ILD患者作为CTD-ILD组，以性别、年龄和体质量指数（BMI）为匹配条件选入45例单纯结缔组织病（CTD）患者（CTD组）和45名健康体检者（对照组）。采用实时荧光定量聚合酶链反应（FQ-PCR）检测EBV-DNA载量，根据检测结果进一步将CTD-ILD患者分为EBV-DNA阳性组（22例）和EBV-DNA阴性组（41例）。通过流式细胞术检测T淋巴细胞亚群水平，采用酶联免疫吸附试验（ELISA）检测血清干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）水平。分析CTD-ILD患者免疫抑制剂使用对患者感染EBV风险的影响。结果 CTD-ILD组、CTD组和对照组EBV-DNA阳性率分别为34.92%（22/63）、17.78%（8/45）和6.67%（3/45），三组间差异有统计学意义（χ2=12.929，P=0.002），且CTD-ILD组EBV-DNA阳性率显著高于CTD组和对照组（P<0.05），CTD组和对照组间比较差异无统计学意义（P>0.05）。免疫抑制剂使用情况未对CTD-ILD患者感染EBV风险造成显著影响（P>0.05）。在CTD-ILD患者中，EBV-DNA阳性组用力肺活量占预计值百分比（FVC% pred）、一氧化碳弥散量占预计值百分比（DLCO% pred）、IFN-γ、CD4+和CD4+/CD8+比值水平低于EBV-DNA阴性组，高分辨率CT（HRCT）评分、IL-4和CD8+水平高于EBV-DNA阴性组，差异有统计学意义（P<0.05）。Pearson相关分析结果显示，CTD-ILD患者IL-4与FVC% pred和DLCO% pred呈负相关（P<0.05），与HRCT评分呈正相关（P<0.05）；IFN-γ、CD4+、CD4+/CD8+比值与FVC% pred和DLCO% pred呈正相关（P<0.05），与HRCT评分呈负相关（P<0.05）。结论 EBV感染与CTD-ILD患者肺间质纤维化严重程度密切相关，其机制可能与免疫失衡及持续性炎症有关。 |
| 关键词: 结缔组织病相关间质性肺疾病 EB病毒 T淋巴细胞 免疫失衡 |
| DOI：10.3969/j.issn.1674-3806.2025.11.11 |
| 分类号:R 563.9 |
| 基金项目:湖北省卫生健康委员会项目（编号：WJ2023F071） |
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| Study on association of Epstein-Barr virus infection with the severity of connective tissue disease-associated interstitial lung disease and immune dysregulation |
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MA Qiao1, HUANG Xin1, ZENG Xiansheng2
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1.School of Medicine, Department of Medicine, Wuhan University of Science and Technology, Wuhan 430065, China; 2.Department of Respiratory and Critical Care Medicine, Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science, Xiangyang 441021, China
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| Abstract: |
| ［Abstract］ Objective To investigate the association of Epstein-Barr virus(EBV) infection with the severity of connective tissue disease-associated interstitial lung disease(CTD-ILD) and immune dysregulation. Methods A retrospective analysis was conducted on the clinical data of 63 CTD-ILD patients(CTD-ILD group) who were admitted to Xiangyang Central Hospital Affiliated to Hubei University of Arts and Science from September 2023 to January 2025. Forty-five patients with connective tissue disease(CTD)(CTD group) and 45 healthy individuals undergoing physical examinations(control group) were selected according to the matching criteria including gender, age, and body mass index(BMI). The EBV-DNA load was detected by using real-time fluorescence quantitative polymerase chain reaction(FQ-PCR). According to the detection results, the CTD-ILD patients were further divided into EBV-DNA positive group(22 patients) and EBV-DNA negative group(41 patients). The levels of T lymphocyte subsets were detected by using flow cytometry, and the levels of serum interferon -γ(IFN-γ) and interleukin-4(IL-4) were detected by using enzyme-linked immunosorbent assay(ELISA). The effect of the use of immunosuppressants on the risk of EBV infection in the CTD-ILD patients was analyzed. Results The positive rates of EBV-DNA in the CTD-ILD group, the CTD group and the control group were 34.92%(22/63), 17.78%(8/45) and 6.67%(3/45), respectively, with statistically significant differences among the three groups(χ2=12.929 P=0.002). The positive rate of EBV-DNA in the CTD-ILD group was significantly higher than that in the CTD group and the control group(P<0.05), while there was no statistically significant difference in the positive rate of EBV-DNA between the CTD group and the control group(P>0.05). The use of immunosuppressants did not significantly affect the risk of EBV infection in the CTD-ILD patients(P>0.05). In the CTD-ILD patients, the levels of forced vital capacity percent predicted(FVC% pred), percent predicted diffusing capacity of the lung for carbon monoxide(DLCO% pred), IFN-γ, CD4+ and CD4+/CD8+ ratio in the EBV-DNA positive group were lower than those in the EBV-DNA negative group, while the high-resolution computed tomography(HRCT) scores, IL-4 and CD8+ levels in the EBV-DNA positive group were higher than those in the EBV-DNA negative group, with statistically significant differences between the two groups(P<0.05). The results of Pearson correlation analysis showed that in the CTD-ILD patients, IL-4 was negatively correlated with FVC% pred and DLCO% pred(P<0.05), and positively correlated with HRCT scores(P<0.05), and the IFN-γ, CD4+ and CD4+/CD8+ ratio were positively correlated with FVC% pred and DLCO% pred(P<0.05), and negatively correlated with HRCT scores(P<0.05). Conclusion EBV infection is closely related to the severity of pulmonary interstitial fibrosis in CTD-ILD patients, and the mechanism may be related to immune dysregulation and persistent inflammation. |
| Key words: Connective tissue disease-associated interstitial lung disease(CTD-ILD) Epstein-Barr virus(EBV) T lymphocyte Immune dysregulation |
