Narjes Soleimanifar; Sara Assaadiasl; Mohammed Sameer Al-Shammari; Abdol-Rahman Rostamian; Maryam Sadr; Sepideh Shahkarami; Hanieh Mojtahedi; Mohammad Hossein Nicknam
Abstract
Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of ...
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Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis. Objective: To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease. Methods: 30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR. Results: The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed. Conclusion: The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.
Nadiah Abu; Nurul Ainaa Adilah Rus Bakarurraini; Siti Nurmi Nasir; Muhiddin Ishak; Rashidah Baharuddin; Rahman Jamal; Nurul Syakima Ab Mutalib
Abstract
Background: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies ...
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Background: Cancer testis antigens (CTAs) are a class of immune-stimulating antigens often overexpressed in many types of cancers. The usage of the CTAs as immunotherapy targets have been widely investigated in different cancers including melanoma, hematological malignancies, and colorectal cancer. Studies have indicated that the epigenetic regulation of the CTAs such as the methylation status may affect the expression of the CTAs. However, the report on the methylation status of the CTAs is conflicting. The general methylation profile of the CTAs, especially in colorectal cancer, is still elusive.Objective: To determine the methylation profile of the selected CTAs in our colorectal cancer patients.Methods: A total of 54 pairs of colorectal cancer samples were subjected to DNA methylation profiling using the Infinium Human Methylation 450K bead chip.Results: We found that most of the CTAs were hypomethylated, and CCNA1 and TMEM108 genes were among the few CTAs that were hypermethylated.Conclusion: Overall, our brief report has managed to show the overall methylation profile in over the 200 CTAs in colorectal cancer and this could be used for further refining any immunotherapy targets.
