Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection
Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficu...
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| Published in | The Journal of experimental medicine Vol. 217; no. 11 |
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| Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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United States
Rockefeller University Press
02.11.2020
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| Abstract | Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms. |
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| AbstractList | Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms. Diagnosis of EBV-driven T/NK-cell lymphoproliferative disorders and chronic active EBV diseases is often difficult. Fournier et al. report a flow-FISH cytometry assay allowing rapid identification of EBV-infected cells in blood and accurate diagnoses. It represents a powerful tool to study pathophysiological mechanisms of EBV-LPD. Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms. Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms. |
| Author | Galicier, Lionel Miot, Charline Barlogis, Vincent Neven, Bénédicte Castelle, Martin Ehl, Stephan Moshous, Despina Latour, Sylvain Molina, Thierry Boutboul, David Winter, Sarah Malphettes, Marion Suarez, Felipe Fischer, Alain Fournier, Benjamin Pellier, Isabelle Delecluse, Henri-Jacques Boulanger, Cécile Picard, Capucine Dunogué, Bertrand Bruneau, Julie Blanche, Stéphane Terrier, Benjamin |
| AuthorAffiliation | 3 Department of Clinical Immunology, Saint-Louis Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France 7 Department of Internal Medicine, Cochin Hospital, National Referral Centre for Systemic and Autoimmune Diseases, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France 10 Unit F100, Institut National de la Santé et de la Recherche Médicale U1074, Deutsches Krebsforschungszentrum, German Cancer Research Center, Heidelberg, Germany 11 Study Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France 13 Department of Pediatric Hematology-Oncology, La Timone Hospital, Marseille, France 14 Collège de France, Paris, France 5 Department of Pediatric Immunology Hematology and Oncology, University Hospital, Angers, France 12 Institute for Immunodeficiency-Center for Chronic Immunodeficiency, Department of Pediatrics and Adolescent Medicine, Medical Center - Faculty of Medicine, University of Freiburg, Germany 2 |
| AuthorAffiliation_xml | – name: 15 Institut National de la Santé et de la Recherche Médicale UMR 1163, Paris, France – name: 3 Department of Clinical Immunology, Saint-Louis Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France – name: 1 Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et de la Recherche Médicale UMR 1163, Imagine Institute, Paris, France – name: 14 Collège de France, Paris, France – name: 8 Department of Adult Hematology, Necker-Enfants Malades Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France – name: 4 Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France – name: 2 Université de Paris, Paris, France – name: 12 Institute for Immunodeficiency-Center for Chronic Immunodeficiency, Department of Pediatrics and Adolescent Medicine, Medical Center - Faculty of Medicine, University of Freiburg, Germany – name: 5 Department of Pediatric Immunology Hematology and Oncology, University Hospital, Angers, France – name: 7 Department of Internal Medicine, Cochin Hospital, National Referral Centre for Systemic and Autoimmune Diseases, Cochin Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France – name: 9 Department of Pediatric Immunology, Hematology and Rheumatology, Necker-Enfants Malades Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France – name: 6 Institut Roi Albert II, Cancerology and Hematology Departments, University Clinics Saint-Luc Hospital, Brussels, Belgium – name: 11 Study Center for Primary Immunodeficiencies, Necker-Enfants Malades Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France – name: 13 Department of Pediatric Hematology-Oncology, La Timone Hospital, Marseille, France – name: 10 Unit F100, Institut National de la Santé et de la Recherche Médicale U1074, Deutsches Krebsforschungszentrum, German Cancer Research Center, Heidelberg, Germany |
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| Copyright | 2020 Fournier et al. Distributed under a Creative Commons Attribution 4.0 International License 2020 Fournier et al. 2020 |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Disclosures: B. Terrier reported personal fees from AstraZeneca, GlaxoSmithKline, Roche/Chugai, and Vifor Pharma outside the submitted work. L. Galicier reported personal fees from Lilly and VIREOTEAM and nonfinancial support from EUSA Pharma, Overcome, and Janssen-Cilag outside the submitted work. No other disclosures were reported. |
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Infect. Dis doi: 10.1086/491740 |
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| Snippet | Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells... Diagnosis of EBV-driven T/NK-cell lymphoproliferative disorders and chronic active EBV diseases is often difficult. Fournier et al. report a flow-FISH... |
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| SubjectTerms | Adult B-Lymphocytes - metabolism B-Lymphocytes - virology Child Child, Preschool Chronic Disease Epstein-Barr Virus Infections - blood Epstein-Barr Virus Infections - complications Epstein-Barr Virus Infections - diagnosis Epstein-Barr Virus Infections - virology Female Flow Cytometry - methods Herpesvirus 4, Human - metabolism Humans Immunodeficiency In Situ Hybridization, Fluorescence - methods Infectious disease and host defense Killer Cells, Natural - metabolism Killer Cells, Natural - virology Leukemia & Lymphoma Life Sciences Lymphoproliferative Disorders - blood Lymphoproliferative Disorders - diagnosis Lymphoproliferative Disorders - etiology Male Phenotype RNA, Viral - analysis RNA, Viral - metabolism T-Lymphocytes - metabolism T-Lymphocytes - virology Technical Advances and Resources Viral Load |
| Title | Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection |
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