Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients
ABSTRACTBackground Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies, secreted by overactivated B cells, directed against self-red blood cells, resulting in hemolysis. It found that aberrant DNA methylation in B cells can induce the production of autoantibodies. Therefore, we attempted...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Hematology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16078454.2023.2240138 |
| _version_ | 1827892082563350528 |
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| author | Manjun Zhao Yang Zhang Jin Yang Lei Chen Ziying Zhang Huaquan Wang Zonghong Shao Limin Xing |
| author_facet | Manjun Zhao Yang Zhang Jin Yang Lei Chen Ziying Zhang Huaquan Wang Zonghong Shao Limin Xing |
| author_sort | Manjun Zhao |
| collection | DOAJ |
| description | ABSTRACTBackground Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies, secreted by overactivated B cells, directed against self-red blood cells, resulting in hemolysis. It found that aberrant DNA methylation in B cells can induce the production of autoantibodies. Therefore, we attempted to explore if similar aberrant DNA methylation occur in AIHA patients.Methods A 49-year-old female wAIHA patient and a 47-year-old female healthy control (HC) were enrolled. Peripheral blood (PB) B cells DNA was extracted. After constructing genomic libraries, bisulfite genomic sequencing (BSP) and DNA methylation profiles were analyzed. BSP was verified using PB B cells from 10 patients with hemolysis, 10 patients with hemolytic remission, and 10 healthy controls (HCs) by Methylation-specific PCR.Results Total DNA methylation of whole-genome C bases (4.8%) and CG type bases (76.8%) in wAIHA patient were lower than those in the HC (5.3 and 82.5%, respectively) (p = 0.022 and p < 0.001). DNA methylation of C bases and CG type bases in whole-genome regulatory elements, such as coding sequence, up2Kb and down2Kb in the patient were also lower than those in the HC (p = 0.041, p = 0.038, and p = 0.029). 30,180 DNA-methylated regions (DMRs) on all 23 chromosomes were identified. DMR-related genes were mainly involved in the Rap1, phospholipase D, HIF-1, calcium, vascular endothelial growth factor (VEGF) and Ras signaling pathways.Conclusion The DNA methylation spectrum of B cells in AIHA patients is different from that of HC, and the proportion of hypo-methylation regions is higher than that of HC. DMR-related genes are mainly related to some signaling pathways. |
| first_indexed | 2024-03-12T21:34:31Z |
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| institution | Directory Open Access Journal |
| issn | 1607-8454 |
| language | English |
| last_indexed | 2024-03-12T21:34:31Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hematology |
| spelling | doaj.art-6d56066eb3ee4c1eb4026e6ea0c94edd2023-07-27T11:34:38ZengTaylor & Francis GroupHematology1607-84542023-12-0128110.1080/16078454.2023.2240138Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patientsManjun Zhao0Yang Zhang1Jin Yang2Lei Chen3Ziying Zhang4Huaquan Wang5Zonghong Shao6Limin Xing7Department of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin, People’s Republic of ChinaABSTRACTBackground Autoimmune hemolytic anemia (AIHA) is caused by auto-antibodies, secreted by overactivated B cells, directed against self-red blood cells, resulting in hemolysis. It found that aberrant DNA methylation in B cells can induce the production of autoantibodies. Therefore, we attempted to explore if similar aberrant DNA methylation occur in AIHA patients.Methods A 49-year-old female wAIHA patient and a 47-year-old female healthy control (HC) were enrolled. Peripheral blood (PB) B cells DNA was extracted. After constructing genomic libraries, bisulfite genomic sequencing (BSP) and DNA methylation profiles were analyzed. BSP was verified using PB B cells from 10 patients with hemolysis, 10 patients with hemolytic remission, and 10 healthy controls (HCs) by Methylation-specific PCR.Results Total DNA methylation of whole-genome C bases (4.8%) and CG type bases (76.8%) in wAIHA patient were lower than those in the HC (5.3 and 82.5%, respectively) (p = 0.022 and p < 0.001). DNA methylation of C bases and CG type bases in whole-genome regulatory elements, such as coding sequence, up2Kb and down2Kb in the patient were also lower than those in the HC (p = 0.041, p = 0.038, and p = 0.029). 30,180 DNA-methylated regions (DMRs) on all 23 chromosomes were identified. DMR-related genes were mainly involved in the Rap1, phospholipase D, HIF-1, calcium, vascular endothelial growth factor (VEGF) and Ras signaling pathways.Conclusion The DNA methylation spectrum of B cells in AIHA patients is different from that of HC, and the proportion of hypo-methylation regions is higher than that of HC. DMR-related genes are mainly related to some signaling pathways.https://www.tandfonline.com/doi/10.1080/16078454.2023.2240138Warm autoimmune hemolytic anemiaB lymphocytesDNA methylationMethylation-specific PCRBisulfite genomic sequenceAutoimmunity disease |
| spellingShingle | Manjun Zhao Yang Zhang Jin Yang Lei Chen Ziying Zhang Huaquan Wang Zonghong Shao Limin Xing Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients Hematology Warm autoimmune hemolytic anemia B lymphocytes DNA methylation Methylation-specific PCR Bisulfite genomic sequence Autoimmunity disease |
| title | Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients |
| title_full | Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients |
| title_fullStr | Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients |
| title_full_unstemmed | Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients |
| title_short | Genome-wide DNA methylation profiles analysis in primary warm autoimmune hemolytic anemia patients |
| title_sort | genome wide dna methylation profiles analysis in primary warm autoimmune hemolytic anemia patients |
| topic | Warm autoimmune hemolytic anemia B lymphocytes DNA methylation Methylation-specific PCR Bisulfite genomic sequence Autoimmunity disease |
| url | https://www.tandfonline.com/doi/10.1080/16078454.2023.2240138 |
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