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

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.