Study on association of Epstein-Barr virus infection with the severity of connective tissue disease-associated interstitial lung disease and immune dysregulation

MA Qiao; HUANG Xin; ZENG Xiansheng

doi:10.3969/j.issn.1674-3806.2025.11.11

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(x2=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.