Zhenping Chen1, Zhenxing Guo2, Jie Ma3, Jingyao Ma3, Fuhong Liu3, Runhui Wu4. 1. Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China; National Key Discipline of Pediatrics, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China. Electronic address: chenzhenping@outlook.com. 2. Department of Hematology/Oncology, First Hospital of Tsinghua University, Beijing 100016, China. 3. Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China; National Key Discipline of Pediatrics, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China. 4. Beijing Key Laboratory of Pediatric Hematology Oncology, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China; National Key Discipline of Pediatrics, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China; Key Laboratory of Major Diseases in Children, Ministry of Education, Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, 56 Nanlishi Road, Beijing 100045, China. Electronic address: runhuiwu@hotmail.com.
Abstract
AIM: To investigate the status of DNA methylation in the Foxp3 promoter in pediatric ITP patients and assess the role of DNA methylation of Treg cells in the pathogenesis of ITP. METHODS: Quantitative DNA methylation levels of Foxp3 promoter in pediatric ITP patients were detected by MassARRAY EpiTYPER. Methylation levels of Foxp3 promoter were analyzed in ITP patients and normal controls. RESULTS: Significantly higher expression of CpG-2, CpG-3 and CpG-11.12 was observed in ITP patients compared to the controls. A subgroup analysis revealed that persistent and chronic ITP patients exhibited significantly higher CpG-6 expression than in the subgroup of newly diagnosed ITP patients. All patients who represented newly diagnosed ITP at admission were reclassified at later follow-up. In this follow-up subgroup analysis, there were significantly higher levels of CpG-6 in the persistent ITP group than that in the newly diagnosed ITP group. CONCLUSIONS: Our results indicate that defective Treg cell activity identified in ITP might be partially mediated through hypermethylation of CpG sites in the promoter region of Foxp3.
AIM: To investigate the status of DNA methylation in the Foxp3 promoter in pediatric ITPpatients and assess the role of DNA methylation of Treg cells in the pathogenesis of ITP. METHODS: Quantitative DNA methylation levels of Foxp3 promoter in pediatric ITPpatients were detected by MassARRAY EpiTYPER. Methylation levels of Foxp3 promoter were analyzed in ITPpatients and normal controls. RESULTS: Significantly higher expression of CpG-2, CpG-3 and CpG-11.12 was observed in ITPpatients compared to the controls. A subgroup analysis revealed that persistent and chronic ITPpatients exhibited significantly higher CpG-6 expression than in the subgroup of newly diagnosed ITPpatients. All patients who represented newly diagnosed ITP at admission were reclassified at later follow-up. In this follow-up subgroup analysis, there were significantly higher levels of CpG-6 in the persistent ITP group than that in the newly diagnosed ITP group. CONCLUSIONS: Our results indicate that defective Treg cell activity identified in ITP might be partially mediated through hypermethylation of CpG sites in the promoter region of Foxp3.