{"title":"不同甲基化模式预测乙型肝炎病毒再激活患者HBsAg血清转化。","authors":"Jayesh Kumar Sevak, Mojahidul Islam, Gayantika Verma, Anoushka Saxena, Preedia Babu E, Shahana Parveen, Ankur Jindal, Manoj Kumar Sharma, Gayatri Ramakrishna, Syed Naqui Kazim, Shiv Kumar Sarin, Nirupama Trehanpati","doi":"10.1080/08820139.2025.2532630","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) modulates immune epigenetic landscape. Therefore, we investigated immune epigenetic landscape in HBsAg seroconverters and non-seroconverters.</p><p><strong>Methods: </strong>Sixteen rHBV patients including seroconverters (SC, <i>n</i> = 7) and non-seroconverters (NSC, <i>n</i> = 9) at baseline and week 24 were recruited. Age matched naïve chronic hepatitis B patients (nCHBV, <i>n</i> = 7) and healthy controls (HC, <i>n</i> = 6) were also included. PBMCs and plasma were subjected to genome-methylation, gene-expression, immunophenotyping, functionality, and cytokines analysis using Reduced Representation Bisulfite Sequencing (RRBS), qRT-PCR, flow-cytometry, and cytokine-bead-array.</p><p><strong>Results: </strong> In rHBV patients, as compared to nCHBV, there is significant hypomethylation (<i>p</i> < .05) of epigenetic remodellers and immune and metabolic genes like KDM2B, NCOR2 and GATA6, TGF-β, IL-6, IRF8, RPTOR, HK3, specifically at CpG islands. At baseline, HBsAg SC had hypomethylation of KDM2B, COX19, IRF8, TLR5, and hypermethylation of LAG3 compare to NSC. By week-24, SC demonstrated hypomethylation of IL17RA, IFN-γ, TGF-β, STAT5B (<i>p</i> < .05) and correlated with increased plasma IL-6 (<i>p</i> = .009) and decreased LAG3 (<i>p</i> = .01). At baseline and 24 weeks, SC depicted differentiation of HBV-specific CD8+, Tfh, and Th1/17 cells.</p><p><strong>Conclusion: </strong>This study identifies hypomethylation of immune genes suggesting enhanced immune response and viral clearance in SC. Conversely, nCHBV and NSC consistently exhibited hypomethylation of LAG3 and TOX, contributing to immune exhaustion.</p>","PeriodicalId":13387,"journal":{"name":"Immunological Investigations","volume":" ","pages":"1-21"},"PeriodicalIF":2.4000,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients.\",\"authors\":\"Jayesh Kumar Sevak, Mojahidul Islam, Gayantika Verma, Anoushka Saxena, Preedia Babu E, Shahana Parveen, Ankur Jindal, Manoj Kumar Sharma, Gayatri Ramakrishna, Syed Naqui Kazim, Shiv Kumar Sarin, Nirupama Trehanpati\",\"doi\":\"10.1080/08820139.2025.2532630\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hepatitis B virus (HBV) modulates immune epigenetic landscape. Therefore, we investigated immune epigenetic landscape in HBsAg seroconverters and non-seroconverters.</p><p><strong>Methods: </strong>Sixteen rHBV patients including seroconverters (SC, <i>n</i> = 7) and non-seroconverters (NSC, <i>n</i> = 9) at baseline and week 24 were recruited. Age matched naïve chronic hepatitis B patients (nCHBV, <i>n</i> = 7) and healthy controls (HC, <i>n</i> = 6) were also included. PBMCs and plasma were subjected to genome-methylation, gene-expression, immunophenotyping, functionality, and cytokines analysis using Reduced Representation Bisulfite Sequencing (RRBS), qRT-PCR, flow-cytometry, and cytokine-bead-array.</p><p><strong>Results: </strong> In rHBV patients, as compared to nCHBV, there is significant hypomethylation (<i>p</i> < .05) of epigenetic remodellers and immune and metabolic genes like KDM2B, NCOR2 and GATA6, TGF-β, IL-6, IRF8, RPTOR, HK3, specifically at CpG islands. At baseline, HBsAg SC had hypomethylation of KDM2B, COX19, IRF8, TLR5, and hypermethylation of LAG3 compare to NSC. By week-24, SC demonstrated hypomethylation of IL17RA, IFN-γ, TGF-β, STAT5B (<i>p</i> < .05) and correlated with increased plasma IL-6 (<i>p</i> = .009) and decreased LAG3 (<i>p</i> = .01). At baseline and 24 weeks, SC depicted differentiation of HBV-specific CD8+, Tfh, and Th1/17 cells.</p><p><strong>Conclusion: </strong>This study identifies hypomethylation of immune genes suggesting enhanced immune response and viral clearance in SC. Conversely, nCHBV and NSC consistently exhibited hypomethylation of LAG3 and TOX, contributing to immune exhaustion.</p>\",\"PeriodicalId\":13387,\"journal\":{\"name\":\"Immunological Investigations\",\"volume\":\" \",\"pages\":\"1-21\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-07-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunological Investigations\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/08820139.2025.2532630\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunological Investigations","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08820139.2025.2532630","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：乙型肝炎病毒（HBV）调节免疫表观遗传景观。因此，我们研究了乙肝表面抗原转化者和非乙肝表面抗原转化者的免疫表观遗传景观。方法：在基线和第24周招募16例rHBV患者，包括血清转化者（SC, n = 7）和非血清转化者（NSC, n = 9）。年龄匹配naïve慢性乙型肝炎患者（nCHBV, n = 7）和健康对照（HC, n = 6）也被纳入。使用减少亚硫酸氢盐测序（RRBS）、qRT-PCR、流式细胞术和细胞因子头阵列对pbmc和血浆进行基因组甲基化、基因表达、免疫表型、功能和细胞因子分析。结果：与nCHBV患者相比，rHBV患者存在显著的低甲基化（p p p = 0.009）和LAG3降低（p = 0.01）。在基线和24周时，SC描述了hbv特异性CD8+， Tfh和Th1/17细胞的分化。结论：本研究发现SC中免疫基因的低甲基化表明免疫应答和病毒清除增强，相反，nCHBV和NSC一致表现出LAG3和TOX的低甲基化，导致免疫衰竭。
Differential Methylation Patterns Predict HBsAg Seroconversion in Hepatitis B Virus Reactivation Patients.
Background: Hepatitis B virus (HBV) modulates immune epigenetic landscape. Therefore, we investigated immune epigenetic landscape in HBsAg seroconverters and non-seroconverters.
Methods: Sixteen rHBV patients including seroconverters (SC, n = 7) and non-seroconverters (NSC, n = 9) at baseline and week 24 were recruited. Age matched naïve chronic hepatitis B patients (nCHBV, n = 7) and healthy controls (HC, n = 6) were also included. PBMCs and plasma were subjected to genome-methylation, gene-expression, immunophenotyping, functionality, and cytokines analysis using Reduced Representation Bisulfite Sequencing (RRBS), qRT-PCR, flow-cytometry, and cytokine-bead-array.
Results: In rHBV patients, as compared to nCHBV, there is significant hypomethylation (p < .05) of epigenetic remodellers and immune and metabolic genes like KDM2B, NCOR2 and GATA6, TGF-β, IL-6, IRF8, RPTOR, HK3, specifically at CpG islands. At baseline, HBsAg SC had hypomethylation of KDM2B, COX19, IRF8, TLR5, and hypermethylation of LAG3 compare to NSC. By week-24, SC demonstrated hypomethylation of IL17RA, IFN-γ, TGF-β, STAT5B (p < .05) and correlated with increased plasma IL-6 (p = .009) and decreased LAG3 (p = .01). At baseline and 24 weeks, SC depicted differentiation of HBV-specific CD8+, Tfh, and Th1/17 cells.
Conclusion: This study identifies hypomethylation of immune genes suggesting enhanced immune response and viral clearance in SC. Conversely, nCHBV and NSC consistently exhibited hypomethylation of LAG3 and TOX, contributing to immune exhaustion.
期刊介绍：
Disseminating immunological developments on a worldwide basis, Immunological Investigations encompasses all facets of fundamental and applied immunology, including immunohematology and the study of allergies. This journal provides information presented in the form of original research articles and book reviews, giving a truly in-depth examination of the latest advances in molecular and cellular immunology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
