scholarly journals Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1097-1104
Author(s):  
JL Sullivan ◽  
BA Woda ◽  
HG Herrod ◽  
G Koh ◽  
FP Rivara ◽  
...  
Keyword(s):  
Lymph Node ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Viral Infections ◽  
Cytotoxic T Cells ◽  
Peripheral Circulation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Node Architecture ◽  
Epstein Barr

The virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by a benign, generalized histiocytic proliferation, with marked hemophagocytosis associated with systemic viral infections. We have studied the virological and immunopathological events occurring in two children experiencing Epstein-Barr VAHS. Neither of the patients had an underlying immunodeficiency and both recovered from their disease and are completely well one year after follow-up. In each patient, evidence for primary Epstein-Barr virus (EBV) infection was documented with a typical humoral immune response, including IgM antibody directed against virus capsid antigen. EBV was demonstrated in lymphoreticular tissues by electron microscopy and molecular hybridization studies. Permissive EBV infection was suggested by the finding of mature virus particles and linear viral DNA in lymphoreticular tissues. Immunopathological studies demonstrated complete effacement of lymph node architecture by a marked proliferation of immunoblasts in patient 1 and infiltration and effacement of the lymph node architecture with benign-appearing histiocytes in patient 2. Atypical lymphocytes characteristic of acute EBV infection were notably absent in the peripheral blood of both patients and cytotoxic T cells, which normally lyse EBV-infected B cells, were also absent from the peripheral circulation. Our observations suggest that EBV-induced VAHS may be the result of an increased virus burden in the face of immunoregulatory cell imbalances.

scholarly journals Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1097-1104 ◽  
Author(s):  
JL Sullivan ◽  
BA Woda ◽  
HG Herrod ◽  
G Koh ◽  
FP Rivara ◽  
...  
Keyword(s):  
Lymph Node ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Viral Infections ◽  
Cytotoxic T Cells ◽  
Peripheral Circulation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Node Architecture ◽  
Epstein Barr

Abstract The virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by a benign, generalized histiocytic proliferation, with marked hemophagocytosis associated with systemic viral infections. We have studied the virological and immunopathological events occurring in two children experiencing Epstein-Barr VAHS. Neither of the patients had an underlying immunodeficiency and both recovered from their disease and are completely well one year after follow-up. In each patient, evidence for primary Epstein-Barr virus (EBV) infection was documented with a typical humoral immune response, including IgM antibody directed against virus capsid antigen. EBV was demonstrated in lymphoreticular tissues by electron microscopy and molecular hybridization studies. Permissive EBV infection was suggested by the finding of mature virus particles and linear viral DNA in lymphoreticular tissues. Immunopathological studies demonstrated complete effacement of lymph node architecture by a marked proliferation of immunoblasts in patient 1 and infiltration and effacement of the lymph node architecture with benign-appearing histiocytes in patient 2. Atypical lymphocytes characteristic of acute EBV infection were notably absent in the peripheral blood of both patients and cytotoxic T cells, which normally lyse EBV-infected B cells, were also absent from the peripheral circulation. Our observations suggest that EBV-induced VAHS may be the result of an increased virus burden in the face of immunoregulatory cell imbalances.

scholarly journals Selective Induction of Th2-Attracting Chemokines CCL17 and CCL22 in Human B Cells by Latent Membrane Protein 1 of Epstein-Barr Virus

2004 ◽  
Vol 78 (4) ◽  
pp. 1665-1674 ◽  
Author(s):  
Takashi Nakayama ◽  
Kunio Hieshima ◽  
Daisuke Nagakubo ◽  
Emiko Sato ◽  
Masahiro Nakayama ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Epstein Barr Virus ◽  
Cytotoxic T Cells ◽  
Th2 Cells ◽  
Th1 Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT Chemokines are likely to play important roles in the pathophysiology of diseases associated with Epstein-Barr virus (EBV). Here, we have analyzed the repertoire of chemokines expressed by EBV-infected B cells. EBV infection of B cells induced expression of TARC/CCL17 and MDC/CCL22, which are known to attract Th2 cells and regulatory T cells via CCR4, and also upregulated constitutive expression of MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5, which are known to attract Th1 cells and cytotoxic T cells via CCR5. Accordingly, EBV-immortalized B cells secreted these chemokines, especially CCL3, CCL4, and CCL22, in large quantities. EBV infection or stable expression of LMP1 also induced CCL17 and CCL22 in a B-cell line, BJAB. The inhibitors of the TRAF/NF-κB pathway (BAY11-7082) and the p38/ATF2 pathway (SB202190) selectively suppressed the expression of CCL17 and CCL22 in EBV-immortalized B cells and BJAB-LMP1. Consistently, transient-transfection assays using CCL22 promoter-reporter constructs demonstrated that two NF-κB sites and a single AP-1 site were involved in the activation of the CCL22 promoter by LMP1. Finally, serum CCL22 levels were significantly elevated in infectious mononucleosis. Collectively, LMP1 induces CCL17 and CCL22 in EBV-infected B cells via activation of NF-κB and probably ATF2. Production of CCL17 and CCL22, which attract Th2 and regulatory T cells, may help EBV-infected B cells evade immune surveillance by Th1 cells. However, the concomitant production of CCL3, CCL4, and CCL5 by EBV-infected B cells may eventually attract Th1 cells and cytotoxic T cells, leading to elimination of EBV-infected B cells at latency III and to selection of those with limited expression of latent genes.

scholarly journals Clinical Warning of Hemophagocytic Syndrome Caused by Epstein-barr Virus

2020 ◽  
Author(s):  
Jinjin Shi ◽  
Chu Chu ◽  
Min Yu ◽  
Dandan Zhang ◽  
Yuqin Li ◽  
...  
Keyword(s):  
Laboratory Tests ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Manifestations ◽  
Prognostic Indicator ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr ◽  
D Dimer

Abstract Objectives This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

scholarly journals Leucine-Rich Glioma-Inactivated Protein 1 Antibody-Positive Polyradiculopathy Associated with Epstein-Barr Virus Infection

2021 ◽  
pp. 549-554
Author(s):  
Berrin Pelit Uzunalimoğlu ◽  
Abdülhamit Sağlam ◽  
Büşra Şişman ◽  
Sefer Günaydın ◽  
Esen Gül Uzuner ◽  
...  
Keyword(s):  
Lymph Node ◽  
Motor Neurons ◽  
Epstein Barr Virus ◽  
Whole Body ◽  
Reactive Lymphoid Hyperplasia ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Cell Counts ◽  
Epstein Barr

Epstein-Barr virus (EBV) has been associated with a plethora of neurological manifestations including polyneuropathy and polyradiculopathy. A 27-year-old man with a recent upper respiratory system infection presented with difficulty in walking. His neurological examination revealed reduced muscle strength in both proximal and distal lower limb muscles without sensory and autonomic signs. Needle electromyography showed abnormal spontaneous activity and reduced recruitment of motor units in muscles innervated by multiple lumbo-sacral roots. Cerebrospinal examination showed increased protein levels with normal cell counts. While spinal MRI was normal, whole-body CT and PET examination showed disseminated lymph node enlargement. Anti-EBV viral capsid antigen and anti-nuclear antigen IgG but not IgM was positive, whereas EBV PCR was negative in blood. Analysis of inguinal lymph node biopsy showed reactive lymphoid hyperplasia and EBV DNA. Leucine-rich glioma-inactivated protein 1 (LGI1) antibody was found in serum but not in CSF. All clinical, imaging, and electrophysiological findings improved following steroid and intravenous immunoglobulin treatment. These findings suggested the acute involvement of lumbo-sacral spinal roots and/or motor neurons. Purely motor polyradiculopathy has been reported in both EBV-positive and LGI1 antibody-positive patients, and EBV infection is known to precede different autoimmune manifestations. Whether EBV infection may trigger LGI1 autoimmunity and cause involvement of spinal motor roots and/or motor neurons needs to be further studied.

scholarly journals Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus

2020 ◽  
Author(s):  
Jinjin Shi ◽  
Chu Chu ◽  
Min Yu ◽  
Dandan Zhang ◽  
Yuqin Li ◽  
...  
Keyword(s):  
Laboratory Tests ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Manifestations ◽  
Prognostic Indicator ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr ◽  
D Dimer

Abstract Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3 + , CD4 + , CD8 + , NK, and CD3-CD19 + cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively. Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

Epstein-Barr virus LMP1 inhibits the expression of SAP gene and upregulates Th1 cytokines in the pathogenesis of hemophagocytic syndrome

Blood ◽  
2005 ◽  
Vol 106 (9) ◽  
pp. 3090-3096 ◽  
Author(s):  
Huai-Chia Chuang ◽  
Jong-Ding Lay ◽  
Wen-Chuan Hsieh ◽  
Hui-Ching Wang ◽  
Yao Chang ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Epstein Barr Virus ◽  
Cell Activation ◽  
Hemophagocytic Syndrome ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ifn Γ ◽  
Epstein Barr ◽  
Th1 Cytokines

AbstractThe primary infection of Epstein-Barr virus (EBV) may result in fatal infectious mononucleosis or hemophagocytic syndrome (HPS) in 2 diseases; that is, X-linked lymphoproliferative disorder (XLP) and hemophagocytic lymphohistiocytosis (HLH). XLP is linked to mutations of the SAP/SH2D1A gene with dysregulated T-cell activation in response to EBV infection. Patients with sporadic HLH, however, usually have no mutation of the SAP/SH2D1A gene, and EBV latent membrane protein-1 (LMP1) can up-regulate Th1 cytokines in EBV-infected T cells. Since both diseases share common manifestations of HPS, it is important to clarify whether a cross-talk exists between signaling lymphocyte activation molecule (SLAM)–associated protein (SAP) and LMP1-mediated pathways to explain the common pathogenesis of HPS. In this study, no mutation of the SAP/SH2D1A gene at exon 2/3 was detected in 7 HLH cases. Interestingly, EBV LMP1 could transcriptionally inhibit the expression of SAP/SH2D1A and activate downstream molecules ERK and interferon-γ (IFN-γ). LMP1-mediated SAP/ERK/IFN-γ signals appear to act via the TNF receptor–associated factor (TRAF)2,5/nuclear factor κB (NF-κB) pathway, since dominantnegative TRAF2/5 and NF-κB inhibitor could rescue SAP expression and downregulate IFN-γ. Although HLH is genetically distinct from XLP, our data suggest that both diseases share a common signal pathway, through either the mutation or LMP1-mediated suppression of the SAP gene, leading to overt T-cell activation and enhanced Th1 cytokine secretion in response to EBV infection.

scholarly journals Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus

2020 ◽  
Author(s):  
Jinjin Shi ◽  
Chu Chu ◽  
Min Yu ◽  
Dandan Zhang ◽  
Yuqin Li ◽  
...  
Keyword(s):  
Laboratory Tests ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Manifestations ◽  
Prognostic Indicator ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr ◽  
D Dimer

Abstract Objectives: This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1-3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH).Methods: The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively.Results: Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 µg/L, the sensitivity and specificity of D-Dimer was 88.90% and 90.20%, respectively.Conclusion: The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

scholarly journals A case of Epstein Barr virus-associated primary squamous cell carcinoma of stomach

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuki Katsura ◽  
Takehiro Okabayashi ◽  
Kazuhiro Ozaki ◽  
Yuichi Shibuya ◽  
Jun Iwata
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Aortic Lymph Node ◽  
Epstein Barr

Abstract Background Primary squamous cell carcinoma (SCC) of stomach is extremely rare. The pathogenesis of SCC of stomach remains unclear. There is only one report that Epstein Barr virus (EBV) infection may be involved in the pathogenesis of SCC arising in the stomach ever before. Here, we report a case of Epstein Barr virus infection-associated primary SCC of stomach in a 70-year-old woman. She was presented to the referring hospital with hematemesis. Initial endoscopy revealed a bleeding gastric ulcer in the upper part of gastric corpus and the coagulation therapy was followed. After a 3-month follow-up, endoscopy revealed a submucosal tumor-like protrusion instead of an ulcer. Computed tomography revealed a mass in the upper part of stomach and swollen lymph nodes along with the lesser curvature and para-aortic lymph node. Biopsy could not confirm the definitive diagnosis. We performed total gastrectomy with para-aortic lymph node sampling. Histological analysis revealed squamous cell carcinoma with EBV infection with lymph node metastases. Tumor cells were positive for EBV-encoded small RNA (EBER) by in situ hybridization. The postoperative course was uneventful and the patient was discharged on day 11 after the operation. CapeOX was started as adjuvant chemotherapy, and the patient remains alive without recurrence 7 months after surgery. Conclusion This is the first case report of EBV infection-associated primary SCC of the stomach diagnosed by in situ hybridization of EBER. EBV infection may be related to the pathogenesis of primary SCC. Further evidence and studies are required to establish optimal strategy for this rare disease.

scholarly journals Clinical warning of hemophagocytic syndrome caused by Epstein-Barr virus

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Jinjin Shi ◽  
Chu Chu ◽  
Min Yu ◽  
Dandan Zhang ◽  
Yuqin Li ◽  
...  
Keyword(s):  
Laboratory Tests ◽  
Epstein Barr Virus ◽  
Hemophagocytic Syndrome ◽  
Clinical Manifestations ◽  
Prognostic Indicator ◽  
Barr Virus ◽  
Ebv Infection ◽  
Ebv Dna ◽  
Epstein Barr ◽  
D Dimer

Abstract Objectives This study aimed to compare the clinical features and laboratory tests of infectious mononucleosis (IM) and hemophagocytic syndrome (HLH) caused by Epstein-Barr virus (EBV) in 1–3-year-old children and to explore the risk factor of HLH caused by EBV (EBV-HLH). Methods The clinical data of 92 children with EBV infection admitted in our hospital from 2011 to 2019 were collected; 61 cases were diagnosed as EBV-IM, and 31 cases were diagnosed as EBV-HLH. The subjects’ clinical manifestations and laboratory tests were analyzed retrospectively. Results Compared with EBV-IM patients, EBV-HLH patients had longer durations of fever, both before hospitalization and overall, and a higher probability of hepatomegaly. The levels of ALT, AST, LDH, TG, SF, D-Dimer and the plasma EBV DNA load of EBV-HLH patients were significantly higher than those of EBV-IM patients. The absolute values of CD3+, CD4+, CD8+, NK, and CD3-CD19+ cells and IgA and IgM levels of EBV-HLH patients were significantly lower than those of EBV-IM patients. The plasma EBV DNA load was positively correlated with the PT, TT, α-HBDH, AST, LDH, CK, Scr, BUN, UA, TG, and CRP levels in EBV-HLH patients, and the plasma EBV DNA load was positively correlated with the D-Dimer level in the EBV-IM patients. Among the 10 different potential markers, at the cut-off point of 1721.500 μg/L, the sensitivity and specificity of D-Dimer was 88.90 and 90.20%, respectively. Conclusion The D-Dimer level may be a good prognostic indicator of EBV-HLH caused by EBV.

scholarly journals Prevalence of Epstein-Barr virus DNA in tonsillar tissue from patients with chronic tonsillitis in Mexican population

2019 ◽  
Vol 13 (08) ◽  
pp. 764-767
Author(s):  
Luis Renee Gonzalez-Lucano ◽  
Gabriela Vazquez Vasquez-Armenta ◽  
Ana Laura Pereira-Suarez ◽  
Adrian Ramirez-de Arellano ◽  
Saul Ramirez-de los Santos ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Viral Infections ◽  
Close Association ◽  
Chronic Tonsillitis ◽  
Barr Virus ◽  
Ebv Infection ◽  
Inflammatory Processes ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Mexican Patients

Introduction: Epstein-Barr Virus (EBV) infection prevails in underdeveloped and developing countries. The tonsils seem to be candidate replication sites for EBV and some studies have exposed a close association among viral infections and chronic tonsillitis. The objective of this study was identifying the EBV prevalence in Mexican patients who had undergone tonsillectomy because of chronic tonsillitis. Methodology: Frozen tissues and medical records were obtained from 50 Mexican patients. DNA was extracted and subjected to PCR to amplify the EBER-2 region of EBV. Next, the patients were classified according to general and clinical characteristics searching a relation with the EBV-DNA positivity. Results: EBV genome was detected in 46% (23/50) of the analysed tonsil tissues. Trends were found regarding the relationship of viral presence with lower values in terms of age (6.1 ± 2.8 vs 7.6 ± 3.7) , a greater degree of hypertrophy (3.5 ± 0.4 vs 3.0 ± 0.6) and an increase in the number of episodes of tonsillitis (11 ± 7.4 vs 9 ± 6.5). Conclusions: The prevalence found of EBV-DNA positivity in tonsillar tissues from patients diagnosed with chronic tonsillitis , supports the fact that palatine tonsils can be occupied by EBV and highlights the importance of conducting future studies focused on understanding the role of the EBV infection in chronic inflammatory processes in the population involved in this study.

Sign in / Sign up

Export Citation Format

Share Document