Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto's disease? Findings from studies on newly diagnosed patients.

Abstract

Introduction: Epstein-Barr virus (EBV) reactivation is increasingly recognized as a potential exacerbator of autoimmune diseases, including Hashimoto's thyroiditis (HT).

Objectives: This study examined the association between EBV reactivation and intracellular Toll-like receptors (TLRs) expression in newly diagnosed, untreated HT patients. The aim was to determine whether EBV reactivation and specific TLRs (TLR3, TLR7, TLR8, and TLR9) contribute to the pathogenesis and progression of HT.

Patients and methods: A cohort was 54 newly diagnosed, untreated patients with HT and 20 healthy volunteers (HV). Also, the HV were similar in age and gender. Blood samples were collected to assess EBV viral load and intracellular expression levels of TLR3, TLR7, TLR8, and TLR9 using flow cytometry. Specific anti-EBV antibodies (e.g., VCA IgM, VCA IgG, EBNA-1 IgM, EBNA-1 IgG) were measured to identify signs of EBV reactivation, while soluble TLRs (sTLR3, sTLR7, sTLR8, and sTLR9) were quantified in serum using ELISA. Notably, this study's patients with Hashimoto's thyroiditis were not euthyroid, as they exhibited significantly lower TSH levels and elevated fT3 and fT4 levels compared to healthy controls.

Results: Results showed a significant increase in EBV reactivation among HT patients, with 26 of 54 (48.1%) testing positive for EBV DNA, compared to none in the control group. HT patients with reactivated EBV showed significantly higher levels of intracellular expression of TLR3, TLR7, and TLR9, with TLR3+ cells constituting an average of 4.72% of CD4+ lymphocytes compared to 0.69% in the control group, suggesting a potential synergistic effect. In addition, soluble TLR levels were increased in HT patients with reactivated EBV, suggesting a potential role in potentiating autoimmune responses.

Conclusions: These findings highlight the importance of considering both viral reactivation and TLR activity in the treatment of HT. Understanding the interplay between EBV and intracellular TLRs may lead to the development of new therapeutic approaches to mitigate the impact of these factors on disease progression. Further research is warranted to investigate the mechanisms underlying this interaction and its implications for treatment strategies.