T-Track-CMV and QuantiFERON-CMV assays for prediction of protection from CMV reactivation in kidney transplant recipients

Gliga, Smaranda; Korth, Johannes; Krawczyk, Adalbert; Wilde, Benjamin; Horn, Peter A.; Witzke, Oliver; Lindemann, Monika; Fiedler, Melanie

doi:10.1016/j.jcv.2018.06.009

Cited by 37 publications

(28 citation statements)

References 22 publications

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“…The Quantiferon®-CMV assay can predict late-onset CMV disease after primary prophylaxis [10][11][12][13][14][15][16] and spontaneous clearance of CMV DNAemia [12,13,29]; it has also been used in two interventional studies to guide primary [16] or secondary (after treatment for a CMV event) [8] prophylaxis. ELISPOT-based CMV-CMI assays (T-Track CMV® and T-SPOT®-CMV) can also help predict CMV events [17][18][19][20][21][22][23][24][25][26]. It should be noted though that, at the time of this manuscript, these assays are limited to research use only in the US.…”

Section: Discussionmentioning

confidence: 99%

“…Interferon gamma (IFN-γ) released from activated CD8+ T-cells is then quantified via ELISA, allowing for a measure of CMV-specific CD8+ (but not CD4+) T-cell response [8][9][10][11][12][13][14][15][16]. The T-Track CMV® and T-SPOT®-CMV assays first isolate peripheral blood mononuclear cells (PBMC), then expose them to a variety of CMV antigens or lysates; the resulting IFN-γ is quantified via ELISpot allowing for a measure of aggregate CMV-specific CD4+/CD8+ Tcell and NK-cell response, but not its individual components [17][18][19][20][21][22][23][24][25][26]. None of these assays are commercially available in the United States (US).…”

Section: Introductionmentioning

confidence: 99%

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Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

et al. 2020

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Background: Cytomegalovirus (CMV) infection is one of the most common opportunistic infections following organ transplantation, despite administration of CMV prophylaxis. CMV-specific T-cell immunity (TCI) has been associated with reduced rates of CMV infection. We describe for the first time clinical experience using the CMV T-Cell Immunity Panel (CMV-TCIP), a commercially available assay which measures CMV-specific CD4+ and CD8+ Tcell responses, to predict clinically significant CMV events. Methods: Adult (> 18-year-old) patients with CMV-TCIP results and ≥ 1 subsequent assessment for CMV DNAemia were included at Brown University and the University of Maryland Medical Center-affiliated hospitals between 4/ 2017 and 5/2019. A clinically significant CMV event was defined as CMV DNAemia prompting initiation of treatment. We excluded indeterminate results, mostly due to background positivity, allogeneic hematopoetic cell transplant (HCT) recipients, or patients who were continued on antiviral therapy against CMV irrespective of the CMV-TCIP result, because ongoing antiviral therapy could prevent a CMV event. Results: We analyzed 44 samples from 37 patients: 31 were solid organ transplant recipients, 4 had hematologic malignancies, 2 had autoimmune disorders. The CMV-protection receiver operating characteristic (ROC) area under the curve (AUC) was significant for %CMV-specific CD4+ (AUC: 0.78, P < 0.001) and borderline for CD8+ (AUC: 0.66, P = 0.064) T-cells. At a cutoff value of 0.22% CMV-specific CD4+ T-cells, positive predictive value (PPV) for protection against CMV was 85% (95%CI 65-96%), and negative predictive value (NPV) was 67% (95%CI 41-87%). Conclusions: The CMV-TCIP, in particular %CMV-specific CD4+ T-cells, showed good diagnostic performance to predict CMV events. The CMV-TCIP may be a useful test in clinical practice, and merits further validation in larger prospective studies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

et al. 2020

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“…In the majority of SOT patients, IGRAs can be performed at any time before and not earlier than 30 days after the transplant. In SOT experiences, IGRAs were performed before transplant, after transplant before CMV infection, or after CMV infection (Table ) . Positive IGRAs, both before and after SOT, were variably predictive of a lower risk of CMV infection/disease, longer CMV‐free period, spontaneous viral clearance, lower rate of CMV infection recurrence, and lower level of CMV DNAemia.…”

Section: Resultsmentioning

confidence: 99%

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

Girmenia

Lazzarotto

Bonifazi

et al. 2019

Clinical Transplantation

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Cytomegalovirus (CMV) remains a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and solid organ transplantation (SOT) recipients. In view of the uncertainties on the assessment and prevention of CMV infection in both transplant procedures, three Italian scientific societies for HSCT and SOT and for Clinical Microbiology appointed a panel of experts to compose a framework of recommendations. Recommendations were derived from a comprehensive analysis of the scientific literature and from a multidisciplinary consensus conference process. The lack of adequate clinical trials focused on certain

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“…There are two easy to apply assays which are commercially available for measuring the cellular response to CMV viremia but they do not directly determine the number of virus-specific T cells: QuantiFERON CMV, which is a whole blood interferon-gamma release assay based on ELISA technology [22] and T-Track CMV, which is an ELISpot assay [23]. Both assays have been used in initial diagnostic trials to determine diagnostic cutoff values [24,25]. These assays are simple to use but both have the limitation that they only give a rough estimation of T cell activation.…”

Section: Methods For Detection and Quantification Of Virus-specific Tmentioning

confidence: 99%

“…For QuantiFERON CMV, it has been shown that it might provide false-negative results if compared with flow cytometry analysis [10]. And in a comparison between both tests, "T-Track CMV" performed better than "QuantiFERON CMV" [25]. To date, neither test has been investigated in children so it is therefore difficult to rate their diagnostic value for pediatric kidney recipients.…”

Section: Methods For Detection and Quantification Of Virus-specific Tmentioning

confidence: 99%

Virus-specific T cells in pediatric renal transplantation

Ahlenstiel-Grunow

Pape

2020

Pediatr Nephrol

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After pediatric kidney transplantation, immunosuppressive therapy causes an increased risk of severe viral complications, especially from cytomegalovirus (CMV), BK polyomavirus (BKPyV) or Epstein-Barr virus (EBV), and less frequent from adenovirus (ADV). However, suitable predictive markers for the individual outcome of viral infections are missing and the therapeutic management remains a challenge to the success of pediatric kidney transplantation. Virus-specific T cells are known for controlling viral replication and there is growing evidence that virus-specific T cells may serve as a prognostic marker to identify patients at risk for viral complications. This review provides an overview of the usability of virus-specific T cells for improving diagnostic and therapeutic management of viral infections with reference to the necessity of antiviral prophylaxis, timing of pre-emptive therapy, and dosing of immunosuppressive medication after pediatric kidney transplantation. Several studies demonstrated that high levels of virus-specific T cells are associated with decrease of virus load and favorable outcome, whereas lack of virus-specific T cells coincided with virus-induced complications. Accordingly, the additional monitoring of virus-specific T cells aims to personalize the management of antiviral therapy, identify overimmunosuppression, and avoid unnecessary therapeutic interventions. Prospective randomized trials in pediatric kidney recipients comparing standard antiviral and immunosuppressive regimens with T cell-guided therapeutic interventions are needed, before monitoring of virus-specific T cells is implemented in the routine care of pediatric kidney graft recipients.

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T-Track-CMV and QuantiFERON-CMV assays for prediction of protection from CMV reactivation in kidney transplant recipients

Cited by 37 publications

References 22 publications

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

Clinical experience with a novel assay measuring cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity by flow cytometry and intracellular cytokine staining to predict clinically significant CMV events

Assessment and prevention of cytomegalovirus infection in allogeneic hematopoietic stem cell transplant and in solid organ transplant: A multidisciplinary consensus conference by the Italian GITMO, SITO, and AMCLI societies

Virus-specific T cells in pediatric renal transplantation

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