Evaluation of Epstein-Barr Virus–Specific Immunologic Response in Solid Organ Transplant Recipients With an Enzyme-Linked ImmunoSpot Assay

Rittá, Massimo; Costa, Cristina; Sinesi, Franca; Sidoti, Francesca; Nauta, Alessia Di; Mantovani, Samantha; Piceghello, Andrea; Simeone, Salvatore; Ricci, Davide; Boffini, Massimo; Solidoro, Paolo; Baldi, S.; Segoloni, G. P.; Cavallo, Rossana

doi:10.1016/j.transproceed.2013.07.033

Cited by 10 publications

(10 citation statements)

References 16 publications

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“…The fact that we did not observe significantly increased levels of T-cell responses to EBV is consistent with the observation that, in our series, no patient developed EBV-related lymphoproliferations, thus preventing the possibility to assess the predictive value of this analysis. Indeed, our results are in line with the observation that EBV-DNA load is generally high in the first year after transplantation in SOT patients with positive EBV-specific T cell responses, when the risk of EBVdriven lymphoproliferative disorders is high (43). Despite T cell responses to "universal" TAAs can be detected also in patients with early stages of cancer (30,31), no significantly higher levels of T-cells specific for TERT and Survivin were detected at baseline or at the time of diagnosis of cancer in the blood of T and NT patients.…”

Section: Discussionsupporting

confidence: 90%

Biological Predictors of De Novo Tumors in Solid Organ Transplanted Patients During Oncological Surveillance: Potential Role of Circulating TERT mRNA

et al. 2021

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BackgroundDe novo tumors are a major cause of morbidity and mortality after long-term solid organ transplantation. Chronic immunosuppression strongly affects solid organ transplanted (SOT) patients’ immune system by promoting immune evasion strategies and reactivations of viruses with oncogenic potential, ultimately leading to cancer onset. In this scenario, an oncological Surveillance Protocol integrated with biobanking of peripheral blood samples and evaluation of immunovirological and molecular parameters was activated for SOT patients at CRO-IRCCS Aviano, with the aim of identifying suitable biomarkers of cancer development.MethodsAn exploratory longitudinal study was designed based on two serial peripheral blood samples collected at least three months apart. Forty nine SOT patients were selected and stratified by tumor onset during follow-up. Spontaneous T-cell responses to EBV, CMV and tumor associated antigens, EBV-DNA and CMV-DNA loads, and circulating TERT mRNA levels were investigated.ResultsSignificantly higher levels of circulating TERT mRNA were observed 3.5-23.5 months before and close to the diagnosis of cancer as compared to tumor-free patients. Plasmatic TERT mRNA levels >97.73 copies/mL at baseline were significantly associated with the risk of developing de novo tumors (HR=4.0, 95%C.I. = 1.4-11.5, p=0.01). In particular, the risk significantly increased by 4% with every ten-unit increment in TERT mRNA (HR=1.04, 95%C.I. = 1.01-1.07, p=0.01).ConclusionsAlthough obtained in an exploratory study, our data support the importance of identifying early biomarkers of tumor onset in SOT patients useful to modulate the pace of surveillance visits.

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Section: Discussionsupporting

confidence: 90%

Biological Predictors of De Novo Tumors in Solid Organ Transplanted Patients During Oncological Surveillance: Potential Role of Circulating TERT mRNA

et al. 2021

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“…Although T cell levels increased after therapeutic reduction of immunosuppressive drugs and rituximab treatment, the magnitude was not different in patients with remission and those requiring additional chemotherapy . Given the still controversial interpretation of EBV loads, further studies of EBV‐specific T cell assays are highly desirable to improve monitoring of patients at risk .…”

Section: Introductionmentioning

confidence: 99%

The “ABC” of Virus-Specific T Cell Immunity in Solid Organ Transplantation

Sester

Leboeuf

Schmidt

et al. 2016

American Journal of Transplantation

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Transplant patients are at increased risk of viral complications due to impaired control of viral replication, resulting from HLA mismatching between graft and host and the immunosuppression needed to avert alloimmune reactions. In the past decade, quantitative viral load measurements have become widely available to identify patients at risk and to inform treatment decisions with respect to immunosuppressive drugs and antiviral therapies. Because viral loads are viewed as the result of viral replication and virus‐specific immune control, virus‐specific T cell monitoring has been explored to optimize management of adenovirus, BK polyomavirus and cytomegalovirus (“ABC”) in transplant patients. Although most studies are descriptive using different technologies, the overall results show that the quantity and quality of virus‐specific T cells inversely correlate with viral replication, whereby strong cellular immune responses are associated with containment of viral replication. The key obstacles to the introduction of assays for virus‐specific T cells into clinical practice is the definition of reliable cutoffs for clinical decision making, the poor negative predictive value of some assays, and the absence of interventional trials justifying changes of antiviral treatment or immunosuppression. More clinical research is needed using optimized assays and targets before standardization and commutability can be envisaged as achieved for viral load testing.

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“…Likewise, monitoring of cell-mediated immunity (CMI) using a Quantiferon-CMV assay may be useful predicting late-onset CMV disease once CMV prophylaxis has been stopped [52]. CMI also have been monitored for EBV using an enzyme-linked immunoSpot assay [53]. Immunoglobulin G (IgG), C3, IgG2 levels, and NK cell counts have been proposed as an attempt to identify the risk of infection in heart transplant recipients within the first year [54].…”

Section: Monitoring Infectionsmentioning

confidence: 99%