<i>Ex vivo</i> monitoring of human cytomegalovirus‐specific CD8+ T‐cell responses using QuantiFERON<sup>®</sup>‐CMV

Walker, Susan; Fazou, Chrysa; Crough, Tania; Holdsworth, Rhonda; Kiely, Philip; Veale, Mary C.; Bell, Scott C.; Gailbraith, A. J.; McNeil, Keith; Jones, S L; Khanna, Rajiv

doi:10.1111/j.1399-3062.2006.00199.x

Cited by 153 publications

(153 citation statements)

References 24 publications

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“…These conclusions are strongly sup- ported by previous studies of other viral infections which have shown that the breadth of the cytotoxic T-lymphocyte response may be important in preventing viral pathogenesis (1,18). Another important implication of this study relates to the potential use of T-cell functional analysis as a diagnostic tool for identifying the levels of virus-specific T-cell responses which would predict the increased or decreased risk of symptomatic HCMV recrudescence (6,7,19). The diagnostic application of this technology will require an extended analysis of a larger cohort of transplant patients in various clinical settings to determine if the protection from HCMV disease in transplant patients is dependent on T-cell responses directed against a broad range of antigens rather than any single antigen.…”

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confidence: 59%

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 ⁺ T-Cell Response

Crough

Fazou

Weiss

et al. 2007

J Virol

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Using ex vivo antigen-specific T-cell analysis, we found that symptomatic cytomegalovirus recrudescence in transplant recipients was coincident with reduced expression of gamma interferon (IFN-␥) by virus-specific CD8؉ T cells and an up-regulation of CD38 expression on these T cells, although there was no significant change in the absolute number of virus-specific cells (as assessed by major histocompatibility complex-peptide multimers). In contrast, HLA class I-matched transplant patients with asymptomatic viral recrudescence showed increased expansion of antigen-specific T cells and highly stable IFN-␥ expression by epitope-specific T cells. These studies suggest that a strong functional T-cell response plays a crucial role in defining the clinical outcome of acute viral recrudescence.The clinical presentation of acute latent viral infections and its interaction with host T-cell responses have recently been investigated in order to understand the dynamics of immune regulation and to develop better therapeutic strategies (5,9,10,20). Previous studies have proposed a role for a number of potential factors, such as viral load and cytokine dysregulation, in controlling the symptoms of acute viral infection (1, 17). It is entirely feasible that the dynamics of emergence of the virus-specific T-cell response during the early stages of viral recrudescence may delimitate the patterns of clinical symptoms in different individuals (11,13,16). Indeed, massive expansion of CD8 ϩ T cells specific for Epstein-Barr virus latent and lytic antigens, which is often a feature of acute EpsteinBarr virus infection, suggests that these T-cell responses are recruited to control the active viral infection (2). However, understanding the biological significance and the longitudinal dynamics of these T cells during acute viral infections in humans is often difficult and is complicated by the nature of immune responses in naturally outbred individual patients. We have addressed some of these limitations by analyzing the dynamics of T-cell responses to a panel of CD8 ϩ T-cell epitopes in a group of HLA class I-matched unrelated human subjects undergoing acute human cytomegalovirus (HCMV) infection with contrasting clinical symptoms. We studied three

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confidence: 59%

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 ⁺ T-Cell Response

Crough

Fazou

Weiss

et al. 2007

J Virol

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“…Both the CMV ELISPOT and CMV-QuantiFERON assays detect IFN-␥ produced by antigen-stimulated peripheral blood mononuclear cells (PBMCs). The main differences between the assays include the antigen stimulus composition, with stimulation of CD8 ϩ T-cell responses in the CMV QuantiFERON assay (21) and stimulation of both CD4 ϩ and CD8 ϩ T-cell responses in the CMV ELISPOT assay (22,23). Moreover, the CMV QuantiFERON assay detects IFN-␥ in a volume of ϳ1 ml of whole blood, while the CMV ELISPOT assay detects IFN-␥ secreted by ϳ2 ϫ 10 5 PBMCs (22,23).…”

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confidence: 99%

Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women

et al. 2016

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Cytomegalovirus (CMV) enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays were examined as potential biomarkers predictive of congenital CMV (cCMV) transmission. Fifty-seven pregnant women with primary CMV infection and 23 with nonprimary CMV infection were recruited in the study. Maternal age, CMV IgG avidity, viremia, and viruria were also included among the potential predictors. Spearman's statistical correlation analysis revealed a positive correlation between the CMV ELISPOT and CMV QuantiFERON assay results (P < 0.001), but only the CMV ELISPOT assay correlated with cCMV (P < 0.001). cCMV was positively correlated with maternal viremia and viruria (P < 0.05) and negatively correlated with CMV IgG avidity (P < 0.01). Maternal age and CMV QuantiFERON assay results were not statistically associated with cCMV. CMV-specific cell-mediated immunity detected by the CMV ELISPOT assay plays a critical role in cCMV. Congenital cytomegalovirus (cCMV) infection affects about 0.7% of newborns worldwide (1-3). The clinical CMV-related sequelae at birth are highly variable and related to maternal serostatus and the time of onset of congenital infection during pregnancy (4-9). Whenever clinically evident, CMV-induced damages include sensorineural hearing loss (SNHL), visual impairment, delayed psychomotorial development, and retardation (10-13). Understanding the risk factors and biomarkers associated with the maternal transmission of CMV infection represents a leading priority for both diagnosis and clinical management of cCMV. Recently, it was shown that maternal CMV cell-mediated immunity (CMI) plays a critical role in determining cCMV (14-16). Several assays are available to assess CMV-specific CMI, and the large majority of these assays are based on interferon gamma (IFN-␥) release assays (IGRAs) (17)(18)(19)(20). In this study, two IGRAs that detect CMV-specific CMI, the CMV enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, were compared for their prediction of cCMV. Both the CMV ELISPOT and CMV-QuantiFERON assays detect IFN-␥ produced by antigen-stimulated peripheral blood mononuclear cells (PBMCs). The main differences between the assays include the antigen stimulus composition, with stimulation of CD8 ϩ T-cell responses in the CMV QuantiFERON assay (21) and stimulation of both CD4 ϩ and CD8 ϩ T-cell responses in the CMV ELISPOT assay (22, 23). Moreover, the CMV QuantiFERON assay detects IFN-␥ in a volume of ϳ1 ml of whole blood, while the CMV ELISPOT assay detects IFN-␥ secreted by ϳ2 ϫ 10 5 PBMCs (22, 23). Recent studies suggest that the CMV ELISPOT and CMV QuantiFERON assays may display large variability on an individual basis (24,25).In order to have a more comprehensive view of the maternal factors associated with cCMV, this study also investigated maternal parameters such as maternal age, viremia, viruria, and CMV immunoglobulin G (IgG) avidity.(The data in this study were partly presented at the Congenital CMV Conference, Brisbane, Australia, 2015.) MATERIALS AND METHOD...

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“…In this study, two interferon gamma (IFN-␥) release assays (IGRA), the CMV enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, widely used to detect pathogenspecific CMI (15)(16)(17)(18)(19)(20)(21), were compared in a group of primarily and nonprimarily CMV-infected pregnant women and in a control group of healthy seropositive and seronegative pregnant and nonpregnant women without evidence of active CMV infection. Several characteristics differ between the CMV ELISPOT and CMV QuantiFERON assays.…”

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confidence: 99%

Comparison of the Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV QuantiFERON Cell-Mediated Immune Assays in CMV-Seropositive and -Seronegative Pregnant and Nonpregnant Women

et al. 2016

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Human cytomegalovirus (CMV) infection is a major cause of congenital infection leading to birth defects and sensorineural anomalies, including deafness. Recently, cell-mediated immunity (CMI) in pregnant women has been shown to correlate with congenital CMV transmission. In this study, two interferon gamma release assays (IGRA), the CMV enzymelinked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, detecting CMV-specific CMI were compared. These assays were performed for 80 CMV-infected (57 primarily and 23 nonprimarily) pregnant women and 115 controls, including 89 healthy CMV-seropositive pregnant women without active CMV infection, 15 CMV-seronegative pregnant women, and 11 seropositive or seronegative nonpregnant women. Statistical tests, including frequency distribution analysis, nonparametric Kruskal-Wallis equality-of-populations rank test, Wilcoxon rank sum test for equality on unmatched data, and lowess smoothing local regression, were employed to determine statistical differences between groups and correlation between the assays. The CMV ELISPOT and CMV QuantiFERON assay data were not normally distributed and did not display equal variance. The CMV ELISPOT but not CMV QuantiFERON assay displayed significant higher values for primarily CMV-infected women than for the healthy seropositive pregnant and nonpregnant groups (P ‫؍‬ 0.0057 and 0.0379, respectively) and those with nonprimary infections (P ‫؍‬ 0.0104). The lowess local regression model comparing the assays on an individual basis showed a value bandwidth of 0.8. Both assays were highly accurate in discriminating CMVseronegative pregnant women. The CMV ELISPOT assay was more effective than CMV-QuantiFERON in differentiating primary from the nonprimary infections. A substantial degree of variability exists between CMV ELISPOT and CMV QuantiFERON assay results for CMV-seropositive pregnant women.

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Ex vivo monitoring of human cytomegalovirus‐specific CD8+ T‐cell responses using QuantiFERON^®‐CMV

Cited by 153 publications

References 24 publications

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 ⁺ T-Cell Response

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 ⁺ T-Cell Response

Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women

Comparison of the Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV QuantiFERON Cell-Mediated Immune Assays in CMV-Seropositive and -Seronegative Pregnant and Nonpregnant Women

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Ex vivo monitoring of human cytomegalovirus‐specific CD8+ T‐cell responses using QuantiFERON®‐CMV

Cited by 153 publications

References 24 publications

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 + T-Cell Response

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 + T-Cell Response

Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women

Comparison of the Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV QuantiFERON Cell-Mediated Immune Assays in CMV-Seropositive and -Seronegative Pregnant and Nonpregnant Women

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Ex vivo monitoring of human cytomegalovirus‐specific CD8+ T‐cell responses using QuantiFERON^®‐CMV

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 ⁺ T-Cell Response

Symptomatic and Asymptomatic Viral Recrudescence in Solid-Organ Transplant Recipients and Its Relationship with the Antigen-Specific CD8 ⁺ T-Cell Response