CTP Synthase 1 Deficiency in Successfully Transplanted Siblings with Combined Immune Deficiency and Chronic Active EBV Infection

Kucuk, Zeynep Yesim; Zhang, Kejian; Filipovich, Lisa; Bleesing, Jack J.

doi:10.1007/s10875-016-0332-z

Cited by 23 publications

(15 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we and others identified immunodeficient patients with a CTPS1 deficiency leading to mainly life-threatening herpes virus infections with varicella-zoster virus (VZV) and EBV. All patients characterized so far have been shown to carry the same homozygous mutation IVS18-1 G>C or NM_001905.3: c.1692-1G>C, p.T566Dfs26X (rs145092287) in the acceptor splice site at introns 17-18, with a likely common ancestor from northwest England (6,(15)(16)(17). In our initial study, we showed that CTPS1 is important for the expansion of activated T cells.…”

Section: Introductionmentioning

confidence: 87%

Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation

Martin¹,

Minet²,

Boschat³

et al. 2020

JCI Insight

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 87%

Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation

Martin¹,

Minet²,

Boschat³

et al. 2020

JCI Insight

View full text Add to dashboard Cite

“…Rare to frequent EBV‐driven B cell lymphoproliferative disorders have been observed in numerous PIDs in which T cell development is not affected or is only moderately affected (ie with normal or low T cell counts in the periphery). These PIDs include deficiencies in STIM1 , NFkB1 , MST1/STK4 , WAS / WASP , DOCK8 , GATA2 , CORO1A , CTPS1, RASGRP1 , and gain‐of‐function (GOF) mutations in PIK3CD and PIK3R1 . The associated gene defects variably impair T‐cell survival, proliferation, migration, synapse formation and/or effector functions, and can also impact other immune cells.…”

Section: Immunodeficiencies Causing Ebv‐driven B‐lymphoproliferative mentioning

confidence: 99%

“…CTPS1 immunodeficiency results from a founder homozygous mutation in CTPS1 , and was originally identified among a population in the north‐west England . Eighteen affected patients have been identified to date (Martin, E. and Latour, S., unpublished data). All the patients experienced recurrent bacterial and viral infections, and most had a severe EBV infection (associated with the occurrence of B‐cell lymphoma in two cases).…”

Section: Immunodeficiencies Causing Ebv‐driven B‐lymphoproliferative mentioning

confidence: 99%

Signaling pathways involved in the T‐cell‐mediated immunity against Epstein‐Barr virus: Lessons from genetic diseases

Latour

Fischer

2019

Immunological Reviews

113

View full text Add to dashboard Cite

Primary immunodeficiencies (PIDs) provide researchers with unique models to understand in vivo immune responses in general and immunity to infections in particular. In humans, impaired immune control of Epstein-Barr virus (EBV) infection is associated with the occurrence of several different immunopathologic conditions; these include non-malignant and malignant B-cell lymphoproliferative disorders, hemophagocytic lymphohistiocytosis (HLH), a severe inflammatory condition, and a chronic acute EBV infection of T cells. Studies of PIDs associated with a predisposition to develop severe, chronic EBV infections have led to the identification of key components of immunity to EBV -notably the central role of T-cell expansion and its regulation in the pathophysiology of EBV-associated diseases. On one hand, the defective expansion of EBV-specific CD8 T cells results from mutations in genes involved in T-cell activation (such as RASGRP1, MAGT1, and ITK), DNA metabolism (CTPS1) or co-stimulatory pathways (CD70, CD27, and TNFSFR9 (also known as CD137/4-1BB)) leads to impaired elimination of proliferating EBV-infected B cells and the occurrence of lymphoma. On the other hand, protracted T-cell expansion and activation after the defective killing of EBV-infected B cells is caused by genetic defects in the components of the lytic granule exocytosis pathway or in the small adapter protein SH2D1A (also known as SAP), a key activator of T-and NK cell-cytotoxicity. In this setting, the persistence of EBV-infected cells results in HLH, a condition characterized by unleashed T-cell and macrophage activation. Moreover, genetic defects causing selective vulnerability to EBV infection have highlighted the role of co-receptor molecules (CD27, CD137, and SLAM-R) selectively involved in immune responses against infected B cells via specific T-B cell interactions. K E Y W O R D S B-cell lymphoproliferation, cell-cytotoxicity, Epstein-Barr virus, hemophagocytic lymphohistiocytosis, primary immunodeficiency, T-cell proliferation | IMMUNE RE S P ON S E S TO EBV INFEC TI ONEpstein-Barr virus (EBV, also known as human herpesvirus 4) is a gamma herpes virus that only infects primates (primarily humans). 1,2 It is an encapsidated, double-stranded DNA virus with more than 100 genes. It is pandemic, since the great majority of human beings (>90%) have been infected by EBV. The main cell target is B lymphocytes that express CD21 -the membrane receptor for EBV entry through its 350 kDa major envelope glycoprotein. In immunocompetent adolescents and adults, EBV infection causes infectious mononucleosis (IM). Immunologically speaking, IM is characterized by a This article is part of a series of reviews covering Signaling and Signal Diversification in Immune

show abstract

“…The etiological factor of myocardial infarction is Epstein-Barr virus (EBV) in most cases, which is characterized by a discrete symptom complex followed by damage of the immune system, namely, the lifetime persistence of the virus in B lymphocytes. EBV is a lymphotropic agent that causes the development of lymphoproliferative syndromes and immune deficiency [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Condition of Lipid Peroxide Oxidation and Antioxidant System in Patients With Infectious Mononucleosis

Shustval

Лядова

Volobueva

et al. 2018

The Journal of v. N. Karazin Kharkiv National University, Series "Medicine"

View full text Add to dashboard Cite

The indicators of the activity of lipid peroxidation and the antioxidant system were studied in dynamics in 158 patients with infectious mononucleosis depending on the severity of the clinical course of the disease. It is proved that lipid peroxidation is significantly activated in patients with infectious mononucleosis as the severity of the disease increases and therefore increases the oxidative activity of blood plasma, the concentration of dyne conjugates and malondialdehyde in the blood, decreases the activity of antioxidant enzymes of erythrocytes (catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase), glutathione peroxidase and glutathione reductase activity in plasma and lowering the concentration of total and reduced glutathione in the blood, as well as reduce the antioxidant activity of blood plasma and erythrocytes. Lipid peroxidation significantly increase and the activity of the antioxidant system decrease in patients with infectious mononucleosis in the acute period of the disease, as evidenced by the increased concentration of dyne conjugates, malonic dialdehyde and total oxidative plasma activity in the blood, reduced activity of the total antioxidant activity of plasma and erythrocytes, the decrease in the activity of antioxidant enzymes of erythrocytes catalase, superoxide dismutase, glutathione peroxidase, glutathione peroxidase and glutathione reductase of blood plasma, the decrease in the concentration of glutathione in the blood. The most pronounced disorders of lipid peroxidation and antioxidant system activity were found in patients with moderate-severe and severe infectious mononucleosis. The development of cytolytic syndrome in infectious mononucleosis is associated with the action of reactive oxygen forms species and lipid hydroperoxide.

show abstract

CTP Synthase 1 Deficiency in Successfully Transplanted Siblings with Combined Immune Deficiency and Chronic Active EBV Infection

Cited by 23 publications

References 3 publications

Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation

Impaired lymphocyte function and differentiation in CTPS1-deficient patients result from a hypomorphic homozygous mutation

Signaling pathways involved in the T‐cell‐mediated immunity against Epstein‐Barr virus: Lessons from genetic diseases

Condition of Lipid Peroxide Oxidation and Antioxidant System in Patients With Infectious Mononucleosis

Contact Info

Product

Resources

About