The impact of cytokine gene polymorphisms on Epstein–Barr virus infection outcome in pediatric liver transplant recipients

Kasztelewicz, Beata; Jankowska, Irena; Pawłowska, Joanna; Teisseyre, Joanna; Dzierżanowska-Fangrat, Katarzyna

doi:10.1016/j.jcv.2012.07.005

Cited by 9 publications

(9 citation statements)

References 36 publications

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“…An increasing body of evidence suggests that polymorphisms of genes involved in immune response could impact the course of herpesviral infection (Sakuma et al 2005, Kasztelewicz et al 2012, Wujcicka et al 2017). In this regard, whether carriers of different allelic variants were more prone to herpesviral infection in AP was assessed.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have also reported a genetic predisposition for herpesviral infection in several inflammatory and malignant diseases (Sakuma et al 2005, Kasztelewicz et al 2012, Wujcicka et al 2017). Given that Herpesviruses have been proposed as putative pathogens in AP (Jakovljevic et al 2018a), it seemed reasonable to explore whether different gene polymorphisms might affect the susceptibility for herpesviral infection in AP.…”

Section: Introductionmentioning

confidence: 92%

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Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?

et al. 2020

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Aim To investigate the possible association between TNFα (−308 G/A) and IL‐1β (−511 C/T) single nucleotide polymorphisms (SNPs) and GSTT and GSTM deletion polymorphisms and risk of apical periodontitis (AP) development, and determine the association of different genotypes with the presence of herpesviral infection in AP. Methodology The study included 120 periapical lesions and 200 control samples. Gene polymorphism analysis was performed using either polymerase chain reaction (PCR) or PCR/ restriction fragment length polymorphism (RFLP). Relative gene expression of TNF‐α and IL‐1β was analysed using reverse transcriptase – real‐time PCR. The presence of Epstein–Barr virus (EBV) and human cytomegalovirus (HCMV) was assessed by nested PCR. Chi‐square and Fisher’s exact tests and logistic regression analyses were done for polymorphisms, whilst Mann–Whitney U‐test was performed for the expression analysis. The expected frequency of variants was analysed by the Hardy–Weinberg equilibrium test. Results TNF‐α (−308 G/A) SNP increased AP susceptibility for heterozygous (odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.06–2.80, P = 0.027) and homozygous (OR = 8.55, 95% CI = 1.77–41.36, P < 0.001) carriers of the variant A allele. On the other hand, IL‐1β (−511 C/T) polymorphism exerted a protective effect both in heterozygotes (OR = 0.540, 95% CI = 0.332–0.880, P = 0.013) and homozygotes (OR = 0.114, 95% CI = 0.026–0.501, P < 0.001). In addition, GSTM1 and GSTT1 null genotypes separately, as well as concomitantly, were associated with an increased risk for AP development (P < 0.001). The null GSTT1 genotype increased approximately twice the risk of Epstein–Barr infection (EBV) in AP (OR = 2.17, 95% CI = 1–4.71, P = 0.048), whilst TNF‐α SNP decreased it, both in heterozygotes (OR = 0.20, 95% CI = 0.08–0.48, P < 0.001) and AA homozygotes (OR = 0.07, 95% CI = 0.01–0.37, P = 0.001). Conclusions GSTM and GSTT deletion polymorphisms, as well as TNFα (−308 G/A) SNP, are associated with increased risk, whereas IL‐1β (−511 C/T) polymorphism decreases the risk of AP development. GSTT and TNFα polymorphisms also appear to modulate the risk of EBV infection in Serbian patients with AP.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?

et al. 2020

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“…Part of the explanation probably lies in the numerous (single-nucleotide) polymorphisms present in the human as well as the viral genome that may affect disease progression at the level of the immune responses and behavior of EBV (Table 1). Recent studies have demonstrated the importance of single nucleotide polymorphisms (SNPs) in cytokines that can influence the outcome of EBV infection in transplant patients [79, 80]. Although a chronically high EBV viral load constitutes a major risk factor for the development of EBV-related lymphoproliferative disorders, not all patients with high EBV serum levels develop symptomatic disease [11].…”

Section: Genetic Studies Gradually Unravel the Molecular Basis Of mentioning

confidence: 99%

“…Although a chronically high EBV viral load constitutes a major risk factor for the development of EBV-related lymphoproliferative disorders, not all patients with high EBV serum levels develop symptomatic disease [11]. IL-1RN (interleukin 1 receptor antagonist) and IL-1 β alleles producing more severe inflammatory responses were found to protect patients against EBV viremia [79]. Analogously, a polymorphism in antiviral IFN-gamma that results in decreased IFN-gamma synthesis has been associated with early-onset and pediatric PTLD [80, 81].…”

Section: Genetic Studies Gradually Unravel the Molecular Basis Of mentioning

confidence: 99%

Molecular Pathogenesis of B-Cell Posttransplant Lymphoproliferative Disorder: What Do We Know So Far?

Morscio

Dierickx

Tousseyn

2013

Clinical and Developmental Immunology

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Posttransplant lymphoproliferative disorder (PTLD) is a potentially fatal disease that arises in 2%–10% of solid organ and hematopoietic stem cell transplants and is most frequently of B-cell origin. This very heterogeneous disorder ranges from benign lymphoproliferations to malignant lymphomas, and despite the clear association with Epstein-Barr Virus (EBV) infection, its etiology is still obscure. Although a number of risk factors have been identified (EBV serostatus, graft type, and immunosuppressive regimen), it is currently not possible to predict which transplant patient will eventually develop PTLD. Genetic studies have linked translocations (involving C-MYC, IGH, BCL-2), various copy number variations, DNA mutations (PIM1, PAX5, C-MYC, RhoH/TTF), and polymorphisms in both the host (IFN-gamma, IL-10, TGF-beta, HLA) and the EBV genome to B-cell PTLD development. Furthermore, the tumor microenvironment seems to play an important role in the course of disease representing a local niche that can allow antitumor immune responses even in an immunocompromised host. Taken together, B-cell PTLD pathogenesis is very complex due to the interplay of many different (patient-dependent) factors and requires thorough molecular analysis for the development of novel tailored therapies. This review aims at giving a global overview of the currently known parameters that contribute to the development of B-cell PTLD.

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“…The ability of EBV to reactivate MSRV is regarded by many as one of the major reasons why the association between the presence of EBV and the development of MS is so strong [67]. Functional polymorphisms in the gene complex responsible for the production of IL-1∃ and IL-12 regulate both individual susceptibility to EBV infection and illness trajectory [68,69]. It is also worthy of note that reactivation of EBV, even if present at a very low titer, leads to the excessive production of inflammatory cytokines and resultant widespread inflammation provoked by the presence of dUTPase, one of the early proteins produced by the replicating virus [70].…”

Section: Epstein-barr Virusmentioning

confidence: 99%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

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Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

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The impact of cytokine gene polymorphisms on Epstein–Barr virus infection outcome in pediatric liver transplant recipients

Cited by 9 publications

References 36 publications

Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?

Association of polymorphisms in TNF‐α, IL‐1β, GSTM and GSTT genes with apical periodontitis: is there a link with herpesviral infection?

Molecular Pathogenesis of B-Cell Posttransplant Lymphoproliferative Disorder: What Do We Know So Far?

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

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