Determination of Epstein-Barr Virus–Infected Lymphocyte Cell Types in Peripheral Blood Mononuclear Cells as a Valuable Diagnostic Tool in Hematological Diseases

Zhang, Peiling; Zeng, Chen; Cheng, Jiali; Zhou, Jing; Gu, Jingmin; Mao, Xia; Zhang, Wei; Cao, Yang; Luo, Hui; Xu, Bin; Li, Qinlu; Xiao, Min; Zhou, Jianfeng

doi:10.1093/ofid/ofz171

Cited by 16 publications

(17 citation statements)

References 36 publications

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“…Because EBERs are abundantly expressed in all infected cells, regardless of the type of latency involved ( Lerner et al, 1981 ), they represent the best markers for detection of EBV presence within cells. Some laboratories have used EBV-specific PCR on sorted cells to detect and characterize circulating EBV-infected cells as an alternative to conventional histology ( Zhang et al, 2019 ), but this approach is cumbersome and may lead to false-positive findings through contamination of the T or NK cell or non–B cell fraction by either infected B cells or plasma EBV DNA, as shown herein in Fig. S4 .…”

Section: Discussionmentioning

confidence: 99%

Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

Fournier

Boutboul

Bruneau

et al. 2020

Journal of Experimental Medicine

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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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Section: Discussionmentioning

confidence: 99%

Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

Fournier

Boutboul

Bruneau

et al. 2020

Journal of Experimental Medicine

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“…Patients who were transplanted at an early age and EBV‐naive may also contribute to high incidence 8 . Patients with non–B‐cell malignancy had a poorer prognosis than those with B‐cell‐type malignancy 9 . In our study, EBV‐DNA level was detected in T, B lymphocytes and NK cells, respectively, in five cases.…”

Section: Discussionmentioning

confidence: 49%

“…8 Patients with non-B-cell malignancy had a poorer prognosis than those with B-cell-type malignancy. 9 In our suggest that a late-onset PTLD is not uncommon. 11 In our study, twothirds of the PTLD cases occurred within one year post-liver transplantation, while Burkitt lymphoma and classical Hodgkin lymphoma cases occurred later than 1.5 years.…”

Section: Discussionmentioning

confidence: 65%

Post‐transplant lymphoproliferative disorder after paediatric liver transplantation

et al. 2020

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Objective The purpose of this study was to analyse the clinical and pathological characteristics, treatments and outcomes of post‐transplant lymphoproliferative disorder (PTLD) in paediatric liver transplant recipients. Method A retrospective analysis of records from nine paediatric liver transplant recipients with PTLD who were treated at our Liver Transplant Center over the period from June 2013 to August 2018. Result Of these nine patients, seven received liver transplantation in our centre and the remaining two patients at other hospitals. The overall incidence of PTLD in paediatric liver transplant recipients in our centre was 1.4% (7/485). The median onset of PTLD after liver transplantation was 11 months. Three cases were classified as infectious mononucleosis PTLD, one case was plasmacytic hyperplasia PTLD, one case was polymorphic PTLD and two cases were Burkitt lymphoma. One case showed diffuse large B‐cell lymphoma and one was classical Hodgkin lymphoma‐like PTLD. These patients presented with different clinical manifestations including fever, anaemia, diarrhoea, hypoproteinaemia, enlargement of lymph nodes, hepatosplenomegaly, jaundice, bowel obstruction and even intestinal perforation. Nine patients were positive for EBV‐DNA in serum. After diagnosis, immunosuppressants were reduced or discontinued in all cases. Eight patients received anti‐CD20 monoclonal antibody (Rituximab) therapy, four cases were treated with a combination of chemotherapy (R‐CHOP, ABVD, COPP/ABV) and one case was combined with radiotherapy. Two cases received surgical treatment due to bowel obstruction. Eight of these patients achieved a complete remission and remained healthy when assessed at the time of final follow‐up. One patient died as a result of PTLD progression. Conclusion PTLD is one of the most serious and fatal complications after liver transplantation. The definitive diagnosis requires histopathology. Treatment varies and basically includes immunosuppression reduction, anti‐CD20 antibody, surgery, radiotherapy and chemotherapy.

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“…B‐cell type infection was not observed in CAEBV but was seen in immunocompromised patients including post‐transplantation states, immunosuppressive medication‐related, EBV + B‐LPDs, EBV + B‐cell lymphomas, and infectious mononucleosis in that study. As CAEBV by definition must occur in immunocompetent individuals, the findings relating B‐cell type EBV infection to immunodeficiency states and infectious mononucleosis provide additional support that this may represent a separate disease and not a phenotypic variant of CAEBV 24 …”

Section: Pathologic Features and Lineage Assessmentmentioning

confidence: 93%

Chronic active Epstein‐Barr virus infection: A heterogeneous entity requiring a high index of suspicion for diagnosis

Ondrejka

Hsi

2020

Int J Lab Hematology

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Chronic active Epstein-Barr virus infection of T-and NK-cell type, systemic form (referred to hereafter as simply CAEBV) is incorporated into the revised WHO 2016 classification scheme within the section of Epstein-Barr virus (EBV)-positive T cell and NK-cell lymphoproliferative diseases of childhood. 1 Complete characteriza-tion of CAEBV has eluded physicians and researchers for decades due to its variable clinical presentations and rates of progression, pathologic overlap with other infectious and inflammatory diseases and systemic lymphomas, a propensity for EBV to infect T-, B-, and NK-cell types, and inconsistent molecular findings that included poly-, oligo-, and monoclonal lymphoproliferations. Despite this heterogeneity, it is important to recognize CAEBV as early as possible in its course, because the disease is intractable and progressive, and a few large series report an all-cause mortality of 30%-44% after 46-68 months, even with varying rates of autologous hematopoietic stem cell transplant. [2][3][4] We present a patient case of CAEBV, and review the history of this unusual disease, its classification and pathologic features, and current themes in pathogenesis and management. | Case summaryA 51-year-old healthy man taking no medications presented with transient skin rash, fever, and pancytopenia which resolved after several days. He was well until one month later, when he developed fever and pancytopenia (WBC 0.6 x 10 9 /L, hemoglobin (Hgb) 117 g/L; platelets (PLT) 77 × 10 9 /L), with slightly elevated liver enzymes, and splenomegaly. A bone marrow biopsy was hypercellular (90%) with an interstitial T cell infiltrate (CD3+, CD2+, CD4+, CD5+, CD7-) identified by flow cytometry and immunohistochemistry. Epstein-Barr viral-encoded RNA by chromogenic in situ hybridization (EBER-CISH) was positive in the lymphocytes (Figure 1). Cytogenetic analysis revealed a normal karyotype. HTLV1/2 antibody screen was nonreactive. PCR studies for T cell receptor gene rearrangement were unsatisfactory due to poor DNA preservation. He was treated with granulocyte colony-stimulating factor (G-CSF), and his white blood cell count improved and symptoms resolved. A bone marrow biopsy was repeated six months later showing low-level involvement by a clonal T cell population (flow cytometry: CD3+, CD4-, CD8-, CD7-, CD26-) which was difficult to appreciate on routine sections. EBER-CISH showed scattered positivity. Clinically, he was asymptomatic and feeling well with nearly normal hematologic parameters (complete blood count: WBC 4.04 × 10 9 /L; Hgb 143 g/L; PLT 113 × 10 9 /L) and minimally elevated aspartate transaminase (AST, 25 U/L) and alanine transaminase (ALT 23 U/L). After 18 months of observation, his leukocyte and platelet counts gradually decreased until he became acutely ill with neutropenic fever, hepatitis, fungemia, and a tooth abscess. He was hospitalized for three weeks with abnormal laboratory parameters: WBC 0.27 × Abstract Chronic active Epstein-Barr virus infection of T-and NK-cell type, systemic form, is a...

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Determination of Epstein-Barr Virus–Infected Lymphocyte Cell Types in Peripheral Blood Mononuclear Cells as a Valuable Diagnostic Tool in Hematological Diseases

Cited by 16 publications

References 36 publications

Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection

Post‐transplant lymphoproliferative disorder after paediatric liver transplantation

Chronic active Epstein‐Barr virus infection: A heterogeneous entity requiring a high index of suspicion for diagnosis

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