The evaluation of Sirtuin, Sestrin2 levels, and the KEAP1/NRF2 signaling pathway in autoimmune thyroiditis

ŞAHBUDAK BN. THE EVALUATION OF SIRTUIN, SESTRIN2 LEVELS, AND THE KEAP1/NRF2 SIGNALING PATHWAY IN AUTOIMMUNE THYROIDITIS. GAZIANTEP UNIVERSITY FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, SPECIALTY THESIS, GAZIANTEP, 2025. Objective: This study aimed to evaluate the levels of Sirtuin1, Sestrin2, and components of the Keap1/Nrf2 signaling pathway in individuals with autoimmune thyroid diseases (Hashiomoto's thyroiditis and Graves' disease), and to investigate their associations with oxidative stress and inflammatory markers. Materials and Methods: A total of 94 patients (diagnosed with Hashiomato's thyroiditis or Graves' disease) aged 18–65 years and 52 healthy control individuals were included in the study. Participants with BMI >30, systemic diseases (e.g., diabetes mellitus, hypertension, malignancy), or pregnancy were excluded. Biochemical parameters, complete blood count, HbA1c, autoimmune markers (anti-TPO, TRAb), inflammatory markers (CRP, ESR), and levels of Sirtuin1, Sestrin2, Keap1, and Nrf2 were evaluated. Carotid intima-media thickness (CIMT) was measured via ultrasonography, and blood pressure recordings were obtained. Results: CIMT was significantly higher in the control group compared to the Graves group. NLR (neutrophil-to-lymphocyte ratio) was elevated in both the Hashiomoto and Graves groups compared to healthy controls. In the Hashiomoto group, Sestrin2 and Keap1 levels showed significant differences. In the Graves group, Sirtuin1 levels were markedly decreased, possibly associated with activation of the NF-κB pathway. Significant correlations were observed between oxidative stress markers and CRP, ESR, triglycerides, and white blood cell counts. Oxidative stress markers were also significantly associated with CIMT, TRAb, and anti-TPO antibody levels. Conclusion: In autoimmune thyroid diseases—particularly Hashiomoto's thyroiditis—markers related to oxidative stress and inflammation, such as Keap1/Nrf2 pathway, Sirtuin1, and Sestrin2, show significant alterations. These biomarkers may reflect early vascular damage (CIMT) and inflammatory processes, and may have clinical relevance for prognosis and therapeutic planning. Keywords: Hashiomoto, Graves, Keap1/Nrf2, Sirtuin1, Sestrin2,