Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies
Abstract Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-44387-5 |
| _version_ | 1797355677188882432 |
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| author | A. Das G. Ariyakumar N. Gupta S. Kamdar A. Barugahare D. Deveson-Lucas S. Gee K. Costeloe M. S. Davey P. Fleming D. L. Gibbons |
| author_facet | A. Das G. Ariyakumar N. Gupta S. Kamdar A. Barugahare D. Deveson-Lucas S. Gee K. Costeloe M. S. Davey P. Fleming D. L. Gibbons |
| author_sort | A. Das |
| collection | DOAJ |
| description | Abstract Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identify a dynamically changing blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and myeloid cell HLA-DR expression, which characterizes sepsis even when the common clinical marker of inflammation, C-reactive protein, is not elevated. Furthermore, single-cell RNA sequencing identifies upregulation of amphiregulin in leukocyte populations during sepsis, which we validate as a plasma analyte that correlates with clinical signs of disease, even when C-reactive protein is normal. This study provides insights into immune pathways associated with early-life sepsis and identifies immune analytes as potential diagnostic adjuncts to standard tests to guide targeted antibiotic prescribing. |
| first_indexed | 2024-03-08T14:14:33Z |
| format | Article |
| id | doaj.art-cf8475e2ea90428da183505fc8574ce4 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-08T14:14:33Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-cf8475e2ea90428da183505fc8574ce42024-01-14T12:29:09ZengNature PortfolioNature Communications2041-17232024-01-0115111510.1038/s41467-023-44387-5Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babiesA. Das0G. Ariyakumar1N. Gupta2S. Kamdar3A. Barugahare4D. Deveson-Lucas5S. Gee6K. Costeloe7M. S. Davey8P. Fleming9D. L. Gibbons10Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, Guy’s HospitalPeter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, Guy’s HospitalDepartment of Neonatology, Evelina London Neonatal Unit, Guy’s and St Thomas’ NHS Foundation TrustPeter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, Guy’s HospitalBioinformatics Platform and Department of Microbiology, Biomedicine Discovery Institute, Monash UniversityBioinformatics Platform and Department of Microbiology, Biomedicine Discovery Institute, Monash UniversityPeter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, Guy’s HospitalBarts and the London School of Medicine and Dentistry, Queen Mary University of LondonInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash UniversityBarts and the London School of Medicine and Dentistry, Queen Mary University of LondonPeter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King’s College London, Guy’s HospitalAbstract Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identify a dynamically changing blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and myeloid cell HLA-DR expression, which characterizes sepsis even when the common clinical marker of inflammation, C-reactive protein, is not elevated. Furthermore, single-cell RNA sequencing identifies upregulation of amphiregulin in leukocyte populations during sepsis, which we validate as a plasma analyte that correlates with clinical signs of disease, even when C-reactive protein is normal. This study provides insights into immune pathways associated with early-life sepsis and identifies immune analytes as potential diagnostic adjuncts to standard tests to guide targeted antibiotic prescribing.https://doi.org/10.1038/s41467-023-44387-5 |
| spellingShingle | A. Das G. Ariyakumar N. Gupta S. Kamdar A. Barugahare D. Deveson-Lucas S. Gee K. Costeloe M. S. Davey P. Fleming D. L. Gibbons Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies Nature Communications |
| title | Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies |
| title_full | Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies |
| title_fullStr | Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies |
| title_full_unstemmed | Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies |
| title_short | Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies |
| title_sort | identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies |
| url | https://doi.org/10.1038/s41467-023-44387-5 |
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