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Project description:Hepatitis B virus (HBV) surface antigen (HBsAg) clearance constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic hepatitis B. Here, we reveal the immunological landscape and mechanism of HBsAg clearance in mice. After acquiring nonopsonized HBsAg, B cells prime CD4+ T cell responses by CCR5- and EBI2-guided interaction with CD4+ T cells at follicular and interfollicular regions, respectively. Monocyte-derived macrophages transport complement-opsonized HBsAg to follicular dendritic cells (FDCs) to maintain germinal center reaction. Batf3+ XCR1+ conventional type 1 DCs (cDC1s) acquire and present HBsAg by MHC-I cross-dressing to drive CD8+ T cell responses in liver. We map the antigen-presenting cell (APC)-T cell crosstalk landscape and identify key costimulatory signals. The immune responses in patients with acute HBV infection are revealed by a single-cell transcriptome atlas. These findings revolutionize our understanding of anti-HBV immune responses and would lead to immunotherapeutic strategies for HBsAg clearance.
2024-07-01 | GSE207541 | GEO
Project description:Hepatitis B virus (HBV) surface antigen (HBsAg) clearance constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic hepatitis B. Here, we reveal the immunological landscape and mechanism of HBsAg clearance in mice. After acquiring nonopsonized HBsAg, B cells prime CD4+ T cell responses by CCR5- and EBI2-guided interaction with CD4+ T cells at follicular and interfollicular regions, respectively. Monocyte-derived macrophages transport complement-opsonized HBsAg to follicular dendritic cells (FDCs) to maintain germinal center reaction. Batf3+ XCR1+ conventional type 1 DCs (cDC1s) acquire and present HBsAg by MHC-I cross-dressing to drive CD8+ T cell responses in liver. We map the antigen-presenting cell (APC)-T cell crosstalk landscape and identify key costimulatory signals. The immune responses in patients with acute HBV infection are revealed by a single-cell transcriptome atlas. These findings revolutionize our understanding of anti-HBV immune responses and would lead to immunotherapeutic strategies for HBsAg clearance.
2024-07-01 | GSE207539 | GEO
Project description:The immune landscape and mechanism of hepatitis B virus surface antigen clearance
| PRJNA856130 | ENA
Project description:The immune landscape and mechanism of hepatitis B virus surface antigen clearance [CITEseq]
| PRJNA856137 | ENA
Project description:The immune landscape and mechanism of hepatitis B virus surface antigen clearance [RNA-Seq]
| PRJNA856138 | ENA
Project description:Owing to similar routes of transmission, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection commonly occurs. Compared with patients infected with only HBV, coinfected patients develop persistent HBV infection followed by advanced liver diseases. However, the characteristics of HIV-infected patients who can achieve the clearance of HBV surface antigen (HBsAg) have not been clarified. In this study, we retrospectively examined patients coinfected with HBV and HIV and determined the host factors associated with HBsAg clearance.Among HIV-infected patients who visited our hospital between 1994 and 2017, we examined medical records of those who were seropositive for HBsAg at least once. Among them, patients who cleared HBsAg afterward were regarded as "cured," while those who remained HBsAg-seropositive until 2017 were "chronic."HBsAg seropositivity was found in 57 patients, and among them, 27 male patients were cured whereas 18 were chronic. The cured patients were significantly younger and had higher CD4 cell and platelet counts than the chronic patients. In addition, the cured patients had higher levels of transaminases after the detection of HBsAg. Multivariate analysis revealed age as an independent factor. Analyses of the patients infected with genotype A also showed that the cured patients had significantly higher CD4 cell counts.Considering that the CD4 cell and platelet counts were higher in the cured patients, immunological and liver functions were closely associated with HBsAg clearance. Higher levels of transaminases in the cured patients may also reflect the immunological function leading to HBsAg clearance.
| S-EPMC7373618 | biostudies-literature
Project description:There are more than 240 million people worldwide chronically infected with HBV, among which, some may develop HBV-related cancer or end stage liver diseases. Lipid disorder remains one of the main mechanisms for chronic liver diseases. To explore the mechanisms induced by hepatitis B surface antigen in lipid disorder, a new pathway was revealed. These findings partially explained how SHBs could promote liver lipid disorder, and may provide a potential new intervention target in HBV related liver diseases.
2020-07-24 | PXD020569 |
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-09-23 | GSE168186 | GEO
Project description:HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic hepatitis B virus infection (CHB). Improved understanding of the clearance correlates of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR HIC), adopting an unbiased approach to the generation of a robust longitudinal data set for adults testing HBsAg positive from a large UK teaching hospital over a 6-year period (2011 to 2016 inclusive). Of 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. Among these 13, the HBsAg clearance rate in individuals on nucleos(t)ide analogue (NA) therapy (n = 4 [31%]; median clearance time,150 weeks) was similar to that in individuals not on NA therapy (n = 9 [69%]; median clearance time, 157 weeks). Those who cleared HBsAg were significantly older and less likely to be on NA therapy than nonclearers (P = 0.003 and P = 0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (P = 0.025). HBeAg clearance occurred in individuals both on NA therapy (n = 24; median time, 49 weeks) and off NA therapy (n = 19; median time, 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematized approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and support improvements in clinical care.IMPORTANCE Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control.
| S-EPMC6593400 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-05-31 | GSE146499 | GEO