scholarly journals X-Linked Lymphoproliferative Disease Presenting as Pancytopenia in a 10-Month-Old Boy

2010 ◽  
Vol 2010 ◽  
pp. 1-3 ◽  
Author(s):  
S. Nicole Chadha ◽  
David Amrol
Keyword(s):  
Immune Responses ◽  
Fulminant Hepatitis ◽  
Epstein Barr Virus ◽  
Genetic Disorder ◽  
Signs And Symptoms ◽  
Lymphoproliferative Disease ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Patient Presentation

X-linked lymphoproliferative disease, also known as Duncan's syndrome, is a rare genetic disorder that causes exaggerated immune responses to Epstein-Barr virus (EBV) infection and often leads to death. Patient presentation varies but can include signs and symptoms typical of EBV, pancytopenia, and fulminant hepatitis.

SH2D1A mutations in Japanese males with severe Epstein-Barr virus–associated illnesses

Blood ◽  
2001 ◽  
Vol 98 (4) ◽  
pp. 1268-1270 ◽  
Author(s):  
Ryo Sumazaki ◽  
Hirokazu Kanegane ◽  
Maki Osaki ◽  
Takashi Fukushima ◽  
Masahiro Tsuchida ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Infectious Mononucleosis ◽  
Epstein Barr Virus ◽  
Genetic Disorder ◽  
Lymphoproliferative Disease ◽  
Barr Virus ◽  
Ebv Infection ◽  
Sporadic Cases ◽  
Epstein Barr ◽  
Acute Infectious Mononucleosis

X-linked lymphoproliferative disease (XLP), a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection, has been linked to mutations in the SH2D1A gene. To search for the occurrence of SH2D1A mutations in Japan, we performed genetic analysis of the SH2D1A gene in 40 males presenting with severe EBV-associated illnesses, including fulminant infectious mononucleosis, EBV-positive lymphoma, and severe chronic active EBV infection. SH2D1A mutations were detected in 10 of these 40 patients. Five of these 10 cases were sporadic. Patients with SH2D1A mutations displayed severe acute infectious mononucleosis with hyperimmunoglobulin M, hypogammaglobulinemia, and B-cell malignant lymphoma. By contrast, chronic active EBV infection was not associated with SH2D1Amutations. XLP survivors exhibited normal levels of circulating EBV-DNA during convalescence, suggesting that SH2D1A protein is not directly responsible for control of EBV replication. Thus, genetic analysis of the SH2D1A gene is particularly useful in the diagnosis of sporadic cases and carriers of XLP.

Human plasmacytoid dendritic cells regulate immune responses to Epstein-Barr virus (EBV) infection and delay EBV-related mortality in humanized NOD-SCID mice

Blood ◽  
2006 ◽  
Vol 109 (3) ◽  
pp. 1043-1050 ◽  
Author(s):  
Wai Hon Lim ◽  
Svjetlana Kireta ◽  
Graeme Randolph Russ ◽  
Patrick Toby Hewlett Coates
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Median Survival ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Scid Mice ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV) is associated with posttransplant lymphoproliferative disease (PTLD), which is a leading cause of cancer death in recipients of transplants. We investigated the role of plasmacytoid dendritic cells (PDCs) in the development of EBV infection and the onset of lymphoproliferative disease (LPD) in humanized NOD-SCID mice and studied the effect of EBV on PDC function. NOD-SCID mice reconstituted with PDC-depleted peripheral blood mononuclear cells (PBMCs) from EBV IgG+ human donors had significantly enhanced mortality from disseminated EBV infection (median survival, 43 days) compared to PBMC-only mice (median survival, 72 days; log-rank P < .05). Mice reconstituted with PDC-enriched PBMCs challenged with EBV exhibited delayed mortality from EBV-LPD (median survival, 80 days) compared to PBMC-only mice challenged with EBV (median survival, 50 days; log-rank P < .05). EBV-stimulated pDCs produced interferon α (IFN-α) and promoted the activation of natural killer cells and IFN-γ–producing CD3+T cells. PDC activation of CD3+T cells in response to EBV stimulation was dependent on cell-to-cell contact, in part mediated by toll-like receptor 9 (TLR-9) signaling that was inhibited by chloroquine and TLR-9 inhibitory CpG. Thus, PDCs play an important role in anti-EBV cellular immune responses that may be targets for manipulation in novel strategies for the treatment of PTLD.

scholarly journals Epstein-Barr virus induced hemophagocytic lymphohistiocytosis in X-linked lymphoproliferative disease

2014 ◽  
Vol 5 (02) ◽  
pp. 171-174 ◽  
Author(s):  
Senthilkumar Sankararaman ◽  
Rosario Maria Riel-Romero ◽  
Majed Jeroudi ◽  
Eduardo Gonzalez-Toledo
Keyword(s):  
Magnetic Resonance ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Epstein Barr Virus ◽  
Genetic Disorder ◽  
Lymphoproliferative Disease ◽  
Specific Pattern ◽  
Resonance Spectroscopy ◽  
Barr Virus ◽  
Epstein Barr ◽  
The Brain

ABSTRACTX-linked lymphoproliferative disease (XLP) is a rare, often fatal genetic disorder characterized by extreme vulnerability to Epstein-Barr virus (EBV). EBV-induced hemophagocytic lymphohistiocytosis (HLH) is a known presentation in XLP. In EBV-induced HLH in XLP, the brain imaging findings in the acute phase include a non specific pattern. In this report, we highlight the magnetic resonance imaging and magnetic resonance spectroscopy findings in a child with EBV induced HLH in XLP.

scholarly journals CAR-T Cells Targeting Epstein-Barr Virus gp350 Validated in a Humanized Mouse Model of EBV Infection and Lymphoproliferative Disease

2020 ◽  
Vol 18 ◽  
pp. 504-524
Author(s):  
Constanze Slabik ◽  
Maja Kalbarczyk ◽  
Simon Danisch ◽  
Reinhard Zeidler ◽  
Frank Klawonn ◽  
...  
Keyword(s):  
T Cells ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Barr Virus ◽  
Ebv Infection ◽  
Car T Cells ◽  
Car T ◽  
Epstein Barr

Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host

Blood ◽  
2004 ◽  
Vol 104 (5) ◽  
pp. 1482-1489 ◽  
Author(s):  
Pierre Rivailler ◽  
Angela Carville ◽  
Amitinder Kaur ◽  
Pasupuleti Rao ◽  
Carol Quink ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Rhesus Macaques ◽  
Humoral Response ◽  
Lymphoproliferative Disease ◽  
Barr Virus ◽  
Ebv Infection ◽  
Oral Inoculation ◽  
Epstein Barr ◽  
Intravenous Inoculation ◽  
Specific Humoral Response

Abstract To develop a model for Epstein-Barr virus (EBV) pathogenesis in immunosuppressed hosts, we studied experimental infections of immunocompetent versus SHIV 89.6P–infected, immunosuppressed rhesus macaques with the EBV-related rhesus lymphocryptovirus (LCV). Primary LCV infection after oral inoculation of 4 immunocompetent animals was characterized by an acute viremia and seroconversion followed by asymptomatic LCV persistence. Four immunosuppressed macaques infected orally with LCV failed to develop an LCV-specific humoral response and viremia was more pronounced, but there was no evidence of LCV-induced lymphoproliferative disease. A more aggressive primary challenge was administered by intravenous inoculation of 108 autologous, LCV-immortalized B cells in 4 additional immunosuppressed animals. Two animals with modest immunosuppression remained asymptomatic, and 1 of 2 severely immunosuppressed animals developed an aggressive, monoclonal LCV-positive lymphoma. These studies demonstrate the potential for lymphomagenesis in an experimental model system for EBV infection and underscore the strength and depth of immune control in limiting LCV-induced lymphoproliferative disease.

scholarly journals Lytic Induction Therapy for Epstein-Barr Virus-Positive B-Cell Lymphomas

2004 ◽  
Vol 78 (4) ◽  
pp. 1893-1902 ◽  
Author(s):  
Wen-hai Feng ◽  
Gregory Hong ◽  
Henri-Jacques Delecluse ◽  
Shannon C. Kenney
Keyword(s):  
B Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Immediate Early ◽  
B Cell Lymphomas ◽  
Lymphoblastoid Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

ABSTRACT A novel therapy for Epstein-Barr virus (EBV)-positive tumors involves the intentional induction of the lytic form of EBV infection combined with ganciclovir (GCV) treatment. Virally encoded kinases (thymidine kinase and BGLF4) which are expressed only during the lytic form of infection convert GCV (a nucleoside analogue) into its active, cytotoxic form. However, tightly latent EBV infection in B cells has made it difficult to identify drugs that can be used clinically to induce lytic viral infection in B-cell lymphomas. Here we demonstrate that gemcitabine and doxorubicin (but not 5-azacytidine, cis-platinum, or 5-fluorouracil) induce lytic EBV infection in EBV-transformed B cells in vitro and in vivo. Gemcitabine and doxorubicin both activated transcription from the promoters of the two viral immediate-early genes, BZLF1 and BRLF1, in EBV-negative B cells. This effect required the EGR-1 motif in the BRLF1 promoter and the CRE (ZII) and MEF-2D (ZI) binding sites in the BZLF1 promoter. GCV enhanced cell killing by gemcitabine or doxorubicin in lymphoblastoid cells transformed with wild-type EBV, but not in lymphoblastoid cells transformed by a mutant virus (with a deletion in the BZLF1 immediate-early gene) that is unable to enter the lytic form of infection. Most importantly, the combination of gemcitabine or doxorubicin and GCV was significantly more effective for the inhibition of EBV-driven lymphoproliferative disease in SCID mice than chemotherapy alone. In contrast, the combination of zidovudine and gemcitabine was no more effective than gemcitabine alone. These results suggest that the addition of GCV to either gemcitabine- or doxorubicin-containing chemotherapy regimens may enhance the therapeutic efficacy of these drugs for EBV-driven lymphoproliferative disease in patients.

scholarly journals Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 288
Author(s):  
Pascal Roland Enok Bonong ◽  
Monica Zahreddine ◽  
Chantal Buteau ◽  
Michel Duval ◽  
Louise Laporte ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systematic Review ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Barr Virus ◽  
Ebv Infection ◽  
Relative Risks ◽  
Epstein Barr

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein–Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92–9.45) and 4.17 (95% CI: 2.61–6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.

scholarly journals Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus

2012 ◽  
Vol 209 (5) ◽  
pp. 913-924 ◽  
Author(s):  
Umaimainthan Palendira ◽  
Carol Low ◽  
Andrew I. Bell ◽  
Cindy S. Ma ◽  
Rachel J.M. Abbott ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Epstein Barr Virus ◽  
Selective Pressure ◽  
Lymphoproliferative Disease ◽  
Effector Memory ◽  
Barr Virus ◽  
Ebv Infection ◽  
Somatic Reversion ◽  
Epstein Barr

Patients with the primary immunodeficiency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8+ T cell subset, displayed a CD45RA−CCR7− effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8+ SAP+ T cells, but not SAP− cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.

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