Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics
Background and aims The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-10-01
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| Series: | eGastroenterology |
| Online Access: | https://egastroenterology.bmj.com/content/2/3/e100067.full |
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| author | Upkar S Gill Patrick T F Kennedy Andrew Hall Rageshri Dhairyawan Alberto Quaglia James M Harris Colin Nixon Fadi Issa Amy Cross Edward Arbe-Barnes Jane A McKeating Dimitra Peppa |
| author_facet | Upkar S Gill Patrick T F Kennedy Andrew Hall Rageshri Dhairyawan Alberto Quaglia James M Harris Colin Nixon Fadi Issa Amy Cross Edward Arbe-Barnes Jane A McKeating Dimitra Peppa |
| author_sort | Upkar S Gill |
| collection | DOAJ |
| description | Background and aims The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection.Method The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions.Results Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses. Shared features including ‘cytotoxicity’ and ‘B cell receptor signalling’ were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of γδT cells in the HDV/HBV sample, were observed within analysed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression.Conclusion This proof-of-principle study shows the value of this platform in investigating the complex immune landscape, highlighting relevant host pathways to disease pathogenesis. |
| format | Article |
| id | doaj-art-fc1ee0e355574540accc5e4589a7d9e0 |
| institution | Kabale University |
| issn | 2766-0125 2976-7296 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | eGastroenterology |
| spelling | doaj-art-fc1ee0e355574540accc5e4589a7d9e02025-01-06T11:35:09ZengBMJ Publishing GroupeGastroenterology2766-01252976-72962024-10-012310.1136/egastro-2024-100067Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomicsUpkar S Gill0Patrick T F Kennedy1Andrew Hall2Rageshri Dhairyawan3Alberto Quaglia4James M Harris5Colin Nixon6Fadi Issa7Amy Cross8Edward Arbe-Barnes9Jane A McKeating10Dimitra Peppa116 Centre for Immunobiology, Barts & The London School of Medicine & Dentistry, QMUL, London, UK6 Centre for Immunobiology, Barts & The London School of Medicine & Dentistry, QMUL, London, UKSurgery, 96th Medical Group, US Air Force Regional Hospital, Eglin AFB, Florida, USA5 Division of Infection and Immunity, Barts Health NHS Trust, London, UK7 UCL Cancer Institute, Royal Free London NHS Foundation Trust, London, UK2 Nuffield Department of Medicine, University of Oxford, Oxford, UK4 Cancer Research UK, Scotalnd Institute, Glasgow, UK1 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK1 Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK3 Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UK2 Nuffield Department of Medicine, University of Oxford, Oxford, UK3 Institute of Immunity and Transplantation, Division of Infection and Immunity, University College London, London, UKBackground and aims The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of hepatitis delta virus (HDV) and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalised treatments. Our aim is to evaluate this method characterising the intrahepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients with hepatitis B virus (HBV) and HDV or HIV co-infection.Method The NanoString GeoMx digital spatial profiling platform was employed to assess expression of HBV surface antigen and CD45 in formalin-fixed paraffin-embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx Human Whole Transcriptome Atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis evaluated transcriptomic signatures across sampled regions.Results Spatially discrete transcriptomic signatures and distinct biological pathways were associated with HBV infection/disease status and immune responses. Shared features including ‘cytotoxicity’ and ‘B cell receptor signalling’ were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of γδT cells in the HDV/HBV sample, were observed within analysed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression.Conclusion This proof-of-principle study shows the value of this platform in investigating the complex immune landscape, highlighting relevant host pathways to disease pathogenesis.https://egastroenterology.bmj.com/content/2/3/e100067.full |
| spellingShingle | Upkar S Gill Patrick T F Kennedy Andrew Hall Rageshri Dhairyawan Alberto Quaglia James M Harris Colin Nixon Fadi Issa Amy Cross Edward Arbe-Barnes Jane A McKeating Dimitra Peppa Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics eGastroenterology |
| title | Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics |
| title_full | Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics |
| title_fullStr | Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics |
| title_full_unstemmed | Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics |
| title_short | Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics |
| title_sort | characterisation of hbv and co infection with hdv and hiv through spatial transcriptomics |
| url | https://egastroenterology.bmj.com/content/2/3/e100067.full |
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