Turk J Immunol. 2023; 11(1): 17-22 | DOI: 10.4274/tji.galenos.2023.70883

The CpG Island Methylation Status and mRNA Expression Level of CTLA4 in Childhood Hashimoto’s Thyroiditis

Fatemeh Saffari¹, Mohammad Hossein Ahmadi², Mehdi Azad², Neda Karami³, Amirhosein Maali⁴, Neda Mohammadi⁵, Ali Homaei⁶, Farshad Foroughi^7
1Department of Pediatrics, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran, Children Growth Research Center, Qazvin University of Medical Sciences, Qazvin, Iran and Research Institute for prevention of Non-communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran
²Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
³Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
⁴Department of Medical Biotechnology, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran and Department of Immunology, Pasteur Institute of Iran, Tehran, Iran
⁵Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
⁶Department of Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
⁷Department of Immunology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran and Cellular and Molecular Research Center, Research Institute for Prevention of non-Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran

Objective: Hashimoto’s thyroiditis (HT) is an autoimmune thyroid disease characterized by thyroid-specific autoantibodies. Recent studies have shown the critical footprint of DNA methylation in autoimmune diseases. The aberrant DNA methylation of CTLA4 has been previously reported in autoimmune thyroid diseases. This study aimed to investigate the methylation status of the CpG island of CTLA4 promoter and its mRNA expression level in HT patients.
Materials and Methods: In this case-control study, 45 HT patients (admitted to Qods Hospital, Qazvin, Iran) and 5 healthy individuals participated. After RNA and DNA extractions, the DNA methylation pattern of the CpG island of CTLA4 promoter and CTLA4 mRNA expression level were evaluated. All statistical analyses were performed using SPSS ver 20.
Results: Our results indicated partial hypermethylation status in the CpG island of CTLA4 promoter in HT patients compared to normal individuals, but this hypermethylation was not significantly higher (p=0.332). The mRNA expression level of CTLA4 was significantly decreased in HT patients compared to that of controls (Foldchange=0.31, p=0.015). Also, serum level of anti-TPO antibody was not significantly correlated with CTLA4 expression level and its methylation status.
Conclusion: Since the CTLA4 acts as an immune checkpoint that leads to the downregulation of immune response, partial hypermethylation and downregulation of CTLA4 may play a critical role in preventing switching off the immune response after a hyperactivation against the thyroid.

Keywords: Autoimmune diseases, Hashimoto disease, CTLA4, DNA methylation, gene expression

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