Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 217, Issue 11, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20192262
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Funding
- Fondation pour la Recherche Medicale [FDM20170638301]
- Ligue Contre le Cancer-Equipe Labelisee (France)
- Institut National de la Sante et de la Recherche Medicale (France)
- French Foundation for Rare Diseases (France)
- Societe Francaise de Lutte contre les Cancers et Leucemies de l'Enfant et de l'Adolescent, AREMIG (France)
- Federation Enfants et Sante (France)
- Institut Imagine [ANR-14-CE14-002801, ANR-18-CE15-0025-01, ANR-10-IAHU-01]
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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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