Cytotoxic T-Lymphocyte-Associated Protein 4 Activity and Epstein-Barr Virus Infection in Thalassemia Patients from Najaf Province: A Cross-Sectional Study

Abstract

Background: Immunological dysregulation secondary to the governing chronic disease burden, repetitive blood transfusions, and ongoing antigenic stimulation exposes patients with thalassemia to enhanced risk of viral persistence or reactivation. Soluble cytotoxic T-lymphocyte-associated protein 4 (sCTLA-4), an important marker associated with immune-checkpoints and physiologically regulating T-cell responses, may be may be elevated due to viral persistence or reactivation of virions that are present as free-floating particles in the serum (also known as viremia) of subjects infected by the Epstein-Barr virus Objective: The aim of this study was evaluation of serum soluble CTLA-4 in thalassemia patients positive and negative for EBV-DNA from Najaf province. Methodology: Cross-sectional study of hundred thalassemia patients. EBV DNA was detected by PCR, while the level of serum soluble CTLA-4 was assessed. This study segregated patients to be either EBV-DNA positive or negative. We analyzed the variables such as age distribution, demographics, clinical features, serum sCTLA-4 levels, logistic regression and correlation, ROC curve. Results: EBV DNA was detected in 45 % of patients. Among patients, EBV-DNA was positive in 56.1% of the population aged between 15–30 years, compared with 30.2% in those aged between 5–15 years. In patients with EBV-DNA, serum soluble CTLA-4 levels were significantly higher than in those without it (56.8 ± 14.9 pg/mL vs 34.7 ± 11.2 pg/mL; P<0.01). Serum sCTLA-4 levels were positively associated with EBV-DNA positivity. Results of logistic regression indicated an increased likelihood of

EBV-DNA testing positive with each 10 pg/mL rise in sCTLA-4. In the ROC study, an area under the curve (AUC) of 0.86 was performed well as a strong classifier. Conclusion: Results: The findings showed that EBV-DNA positive was significantly associated with a high level of serum soluble CTLA-4 in thalassemia patients. Further studies are warranted to confirm serum sCTLA-4 as potential biomarker of EBV-induced immune dysregulation disease of thalassemia, together with quantitative profiling for viral load using an appropriate sampling approach and immunophenotyping.