scholarly journals Multifocal Oral Epstein–Barr Virus-Positive Mucocutaneous Ulcers Associated with Dual Methotrexate and Leflunomide Therapy: A Case Report

2022 ◽  
Author(s):  
Sumana Kunmongkolwut ◽  
Chatchawan Amornkarnjanawat ◽  
Ekarat Phattarataratip
Keyword(s):  
Epstein Barr Virus ◽  
Clinical Findings ◽  
Lymphoid Cells ◽  
Barr Virus ◽  
Immunosuppressive Medications ◽  
Atypical Cells ◽  
Immunosuppressed Patients ◽  
Infected Cells ◽  
Rna In Situ Hybridization ◽  
Epstein Barr

AbstractEpstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unique clinicopathologic entity of lymphoproliferative disorder, occurring in immunosuppressed patients. Due to its rarity, EBVMCU may be under-recognized by clinicians as well as pathologists. In addition, its clinical and histopathologic features overlap with other benign and malignant conditions, making a diagnosis challenging. This report presents an unusual case of multifocal oral EBVMCUs in a 52-year-old female patient with rheumatoid arthritis, receiving the combination of methotrexate and leflunomide for 5 years. The patient presented with persistent multiple large painful ulcers involving her palate and gingiva for 6 months. The histopathologic examination revealed extensive ulceration with diffuse polymorphic inflammatory infiltrate admixed with scattered atypical lymphoid cells showing occasional Hodgkin and Reed/Sternberg-like cell features. These atypical cells showed immunoreactivity for CD20, CD30 and MUM1/IRF4. EBV-encoded small RNA in situ hybridization was positive, validating the presence of EBV-infected cells. Two months after discontinuation of both immunosuppressive medications, oral lesions gradually regressed. At 9-month follow-up, no evidence of relapsing oral EBVMCU has been observed. The multifocal presentation of EBVMCU is rare and could be resulted from the overwhelming immune suppression by long-term use of dual immunosuppressants. Its diagnosis requires comprehensive correlation of patient history, clinical findings, histopathologic, and immunophenotypic features. The ability of EBVMCU to regress following removal of immunosuppressive causes is in drastic contrast to a variety of its potential clinical and histopathologic mimics. Therefore, accurate diagnosis is crucial to avoid unnecessary patient management and achieve optimal patient outcomes.

scholarly journals Epstein-Barr Virus–Infected Resting Memory B Cells, Not Proliferating Lymphoblasts, Accumulate in the Peripheral Blood of Immunosuppressed Patients

1999 ◽  
Vol 190 (4) ◽  
pp. 567-576 ◽  
Author(s):  
Gregory J. Babcock ◽  
Lisa L. Decker ◽  
Richard B. Freeman ◽  
David A. Thorley-Lawson
Keyword(s):  
B Cells ◽  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Memory B Cells ◽  
Barr Virus ◽  
Latently Infected ◽  
Immunosuppressed Patients ◽  
Infected Cells ◽  
Epstein Barr ◽  
Healthy Carriers

When Epstein-Barr virus (EBV) infects B cells in vitro, the result is a proliferating lymphoblast that expresses at least nine latent proteins. It is generally believed that these cells are rigorously controlled in vivo by cytotoxic T cells. Consistent with this, the latently infected cells in the peripheral blood of healthy carriers are not lymphoblasts. Rather, they are resting memory B cells that are probably not subject to direct immunosurveillance by cytotoxic T lymphocytes (CTLs). When patients become immunosuppressed, the viral load increases in the peripheral blood. The expansion of proliferating lymphoblasts due to the suppressed CTL response is believed to account for this increase and is considered to be a major risk factor for posttransplant lymphoproliferative disease (PTLD) and AIDS-associated B cell lymphoma. Here we show that there is an increase in the numbers of latently infected cells in the peripheral blood of immunosuppressed patients. However, the cells are not proliferating lymphoblasts. They are all latently infected, resting, memory B cells—the same population of infected cells found in the blood of healthy carriers. These results are discussed in the context of a model for EBV persistence that explains why PTLD is usually limited to the lymph nodes.

scholarly journals Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus

Blood ◽  
1995 ◽  
Vol 85 (3) ◽  
pp. 744-750 ◽  
Author(s):  
I Anagnostopoulos ◽  
M Hummel ◽  
C Kreschel ◽  
H Stein
Keyword(s):  
Epithelial Cells ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Lymphoid Cells ◽  
Productive Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Infected Cells ◽  
Epstein Barr ◽  
Acute Infectious Mononucleosis

The present study was undertaken to unequivocally demonstrate the morphology, immunophenotype, and localization of Epstein Barr virus (EBV)-infected cells as well as the type of infection (latent versus productive) in tonsils of acute infectious mononucleosis. Paraffin sections from nine cases with clinical, serologic, and morphologic evidence of EBV infection were analyzed for the detection of small transcripts, designated EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using nonisotopically labeled probes. ISH was combined with immunohistology, employing a broad panel of antibodies against B-, T-, epithelial-, macrophage-, and follicular dendritic cell (FDC)-antigens. All EBER-positive cells could be identified as lymphocytes, as they did not exhibit any morphologic or immunologic characteristics of epithelial cells, macrophages, or FDCs. A preferential accumulation of EBER-positive cells was noted around crypts, within surface squamous epithelium, and in the surroundings of necrosis. The majority of these lymphocytes could be shown to be B cells, which morphologically included Reed-Sternberg (RS)-like cells, immunoblasts, medium-sized lymphoid cells, as well as cells with plasmacytoid differentiation. In all cases, a varying number of EBER-positive T cells could be identified. ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle. Such cells could also be detected within the crypt epithelium reaching up to its surface. Additional screening of 123 oropharyngeal mucosa samples from patients without evidence of acute EBV-infection, using the polymerase chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH showed single latently infected lymphocytes in only one case. Our data imply that infected lymphocytes and not epithelial cells are, in fact, the reservoir for EBV infection, and that these are the cells that participate in the interindividual virus transfer.

Studies of Epstein-Barr Virus Antigens Using Immunoperoxidase and Immunofluorescence Techniques

1975 ◽  
Vol 33 ◽  
pp. 342-343
Author(s):  
R. Stephens ◽  
K. Traul ◽  
D. Woolf ◽  
P. Gaudreau
Keyword(s):  
Electron Microscopy ◽  
Nasopharyngeal Carcinoma ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
If Technique ◽  
Infected Cells ◽  
Virus Antigens ◽  
Epstein Barr ◽  
Virus Capsid Antigen ◽  
Antigen Reactivity

A number of antigens have been found associated with persistent EBV infections of lymphoblastoid cells. Identification and localization of these antigens were principally by immunofluorescence (IF) techniques using sera from patients with nasopharyngeal carcinoma (NPC), Burkitt lymphoma (BL), and infectious mononucleosis (IM). Our study was mainly with three of the EBV related antigens, a) virus capsid antigen (VCA), b) membrane antigen (MA), and c) early antigens (EA) using immunoperoxidase (IP) techniques with electron microscopy (EM) to elucidate the sites of reactivity with EBV and EBV infected cells.Prior to labeling with horseradish peroxidase (HRP), sera from NPC, IM, and BL cases were characterized for various reactivities by the indirect IF technique. Modifications of the direct IP procedure described by Shabo and the indirect IP procedure of Leduc were made to enhance penetration of the cells and preservation of antigen reactivity.

Replication of latent Epstein-Barr virus genomes in normal and malignant lymphoid cells

1989 ◽  
Vol 44 (3) ◽  
pp. 560-564 ◽  
Author(s):  
Alice Adams ◽  
Tamara C. Pozos ◽  
Helen V. Purvey
Keyword(s):  
Epstein Barr Virus ◽  
Lymphoid Cells ◽  
Barr Virus ◽  
Epstein Barr ◽  
Virus Genomes

Cytomegalovirus-Associated Hemophagocytic Syndrome

PEDIATRICS ◽  
1985 ◽  
Vol 75 (2) ◽  
pp. 280-283
Author(s):  
ELIZABETH H. DANISH ◽  
BEVERLY B. DAHMS ◽  
MARY L. KUMAR
Keyword(s):  
Viral Infection ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Course ◽  
Underlying Disease ◽  
Barr Virus ◽  
Pathologic Findings ◽  
Immunosuppressed Patients ◽  
Epstein Barr ◽  
Herpes Group

Virus-associated hemophagocytic syndrome, first described by Risdall and co-workers in 1979,1 is a rare histiocytic proliferative syndrome characterzed by fever, hepatosplenomegaly, pancytopenia, and erythrophagocytosis by histiocytes that appear benign by histologic criteria. The clinical course and pathologic findings may be identical with another histiocytic disorder, familial erythrophagocytic lymphohistiocytosis, which occurs predominantly in infants. Diagnosis of virus-associated hemophagocytic syndrome depends entirely on evidence of concurrent viral infection, usually of the herpes group. Epstein-Barr virus has been associated with this syndrome in the few cases reported in children without underlying disease, whereas cytomegalovirus (CMV) has been implicated in immunosuppressed patients. We report a case of fatal CMV-associated hemophagocytic syndrome which occurred in a previously healthy infant.

scholarly journals Identification of Epstein–Barr virus-infected CD27+ memory B-cells in liver or stem cell transplant patients

2011 ◽  
Vol 92 (11) ◽  
pp. 2590-2595 ◽  
Author(s):  
Yoshinori Ito ◽  
Shinji Kawabe ◽  
Seiji Kojima ◽  
Fumihiko Nakamura ◽  
Yukihiro Nishiyama ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Stem Cell ◽  
B Cells ◽  
Epstein Barr Virus ◽  
Peripheral Blood Lymphocytes ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr

To analyse the phenotype of Epstein–Barr virus (EBV)-infected lymphocytes in EBV-associated infections, cells from eight haematopoietic stem cell/liver transplantation recipients with elevated EBV viral loads were examined by a novel quantitative assay designed to identify EBV-infected cells by using a flow cytometric detection of fluorescent in situ hybridization (FISH) assay. By this assay, 0.05–0.78 % of peripheral blood lymphocytes tested positive for EBV, and the EBV-infected cells were CD20+ B-cells in all eight patients. Of the CD20+ EBV-infected lymphocytes, 48–83 % of cells tested IgD positive and 49–100 % of cells tested CD27 positive. Additionally, the number of EBV-infected cells assayed by using FISH was significantly correlated with the EBV-DNA load, as determined by real-time PCR (r 2 = 0.88, P<0.0001). The FISH assay enabled us to characterize EBV-infected cells and perform a quantitative analysis in patients with EBV infection after stem cell/liver transplantation.

scholarly journals Histological and Electron Microscopic Studies of Endemic Ethmoidal Carcinomas in Cattle

1979 ◽  
Vol 16 (2) ◽  
pp. 180-190 ◽  
Author(s):  
A. Pospischil ◽  
T. Haenichen ◽  
H. Schaeffler
Keyword(s):  
Epstein Barr Virus ◽  
Undifferentiated Carcinoma ◽  
Olfactory Mucosa ◽  
Lymphoid Cells ◽  
Electron Microscopic ◽  
Barr Virus ◽  
Human Nasopharyngeal Carcinoma ◽  
Microscopic Studies ◽  
Epstein Barr ◽  
Tumor Types

In five cases of endemic ethmoidal carcinoma in cattle from the Dominican Republic three tumor types could be classified: undifferentiated carcinoma (3), adenocarcinoma (1), and squamous cell carcinoma (1). Electron microscopy showed that the tumor cells in undifferentiated carcinomas closely resembled the cells of the normal olfactory mucosa. This was especially true for the dark cells of Bowman's gland. Ultrastructurally, the lymphoid cells of the undifferentiated bovine carcinoma resembled the lymphoid cells of human nasopharyngeal carcinoma being closely associated with Epstein-Barr Virus. This and epidemiological observations suggested a viral cause of endemic ethmoidal carcinoma.

scholarly journals Epstein–Barr virus induces a distinct form of DNA-bound STAT1 compared with that found in interferon-stimulated B lymphocytes

2007 ◽  
Vol 88 (7) ◽  
pp. 1876-1886 ◽  
Author(s):  
James McLaren ◽  
Martin Rowe ◽  
Paul Brennan
Keyword(s):  
Dna Binding ◽  
Epstein Barr Virus ◽  
Lymphoblastoid Cell Lines ◽  
Distinct Form ◽  
Post Translational Modifications ◽  
Constitutive Activation ◽  
Barr Virus ◽  
Molecular Identity ◽  
Infected Cells ◽  
Epstein Barr

Since ‘constitutive activation’ of STAT1 was first described in Epstein–Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs), there has been controversy regarding the molecular identity of the STAT1 DNA-binding complex found in these cells. The post-translational modifications of STAT1 in LCLs have been analysed and an LMP1-induced STAT1 DNA-binding complex, different from that generated by alpha interferon (IFN) stimulation and not involving tyrosine phosphorylation, is demonstrated. STAT1 is serine-phosphorylated downstream of PI3K and MEK in LCLs and this modification restricts IFN-stimulated STAT1–DNA binding. These data suggest that EBV induces a distinct form of DNA-bound STAT1 in virus-infected cells.

scholarly journals Epstein–Barr Virus Permissively Infects Human Syncytiotrophoblastsin Vitroand Induces Replication of Human T Cell Leukemia-Lymphoma Virus Type I in Dually Infected Cells

Virology ◽  
1997 ◽  
Vol 229 (2) ◽  
pp. 400-414 ◽  
Author(s):  
Ferenc D. Tóth ◽  
George Aboagye-Mathiesen ◽  
József Nemes ◽  
Xiangdong Liu ◽  
István Andirkó ◽  
...  
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Epstein Barr Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Barr Virus ◽  
Human T Cell ◽  
Infected Cells ◽  
Epstein Barr

scholarly journals Infection of Epstein–Barr Virus in Type III Latency Modulates Biogenesis of Exosomes and the Expression Profile of Exosomal miRNAs in the Burkitt Lymphoma Mutu Cell Lines

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 237 ◽  
Author(s):  
Asuka Nanbo ◽  
Harutaka Katano ◽  
Michiyo Kataoka ◽  
Shiho Hoshina ◽  
Tsuyoshi Sekizuka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Burkitt Lymphoma ◽  
Epstein Barr Virus ◽  
Type I ◽  
Type Iii ◽  
Barr Virus ◽  
Ebv Infection ◽  
Latently Infected ◽  
Infected Cells ◽  
Epstein Barr

Infection of Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing. We found that the biogenesis of exosomes is upregulated in type III latently infected cells compared with EBV-negative and type I latently infected cells. We also observed that viral and several specific host microRNAs were predominantly incorporated in the exosomes released from the cells in type III latency. We confirmed that multiple viral microRNAs were transferred to the epithelial cells cocultured with EBV-infected B cells. Our findings indicate that EBV infection, in particular in type III latency, modulates the biogenesis of exosomes and the profile of exosomal microRNAs, potentially contributing to phenotypic changes in cells receiving these exosomes.

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