Diagnostic Utility of Human Cytomegalovirus-Specific T-Cell Response Monitoring in Predicting Viremia in Pediatric Allogeneic Stem-Cell Transplant Patients

Abate, Davide; Cesaro, Simone; Cofano, Simona; Fiscon, Marta; Saldan, Alda; Varotto, Stefania; Mengoli, Carlo; Pillon, Marta; Calore, Elisabetta; Biasolo, Maria Angela; Cusinato, Riccardo; Barzon, Luisa; Messina, Chiara; Carli, Modesto; Palù, Giorgio

doi:10.1097/tp.0b013e31824215db

Cited by 29 publications

(32 citation statements)

References 51 publications

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“…In CMV-seronegative transplant recipients of a CMV-positive donor (D ϩ /R Ϫ ), de novo CMI develops upon primary CMV infection, which often originates from virus reactivation within the allograft, while in CMV-seropositive transplant recipients (R ϩ ), CMI recovers from previously existing immunity. The assessment of CMV-specific CMI has also been used to determine the individual risk of infection and as a helpful indicator in making therapeutic decisions, such as whether to initiate or terminate an antiviral treatment (6)(7)(8)(9)(10)(11)(12). For this reason, a diagnostic test assessing the status of immune reconstitution has been recommended in the current CMV management guidelines for transplant patients (13).…”

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confidence: 99%

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

et al. 2013

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Assessing cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) represents an appealing strategy for identifying transplant recipients at risk of infection. In this study, we compared two gamma interferon-releasing assays (IGRAs), Quantiferon-CMV and CMV enzyme-linked immunosorbent spot (ELISPOT), to determine the ability of each test to predict protective CMVspecific T-cell responses. Two hundred twenty-one Quantiferon-CMV and ELISPOT tests were conducted on 120 adult kidney transplant recipients (KTRs), including 100 CMV-seropositive transplant recipients (R ؉ ) and 20 CMV-seronegative transplant recipients of a CMV-positive donor (D ؉ /R ؊ ). As a control cohort, 39 healthy adult subjects (including 33 CMV-seropositive and 6 CMV-seronegative subjects) were enrolled. CMV IgG serology was used as a reference for both tests. In the CMV-seropositive individuals, the ELISPOT and Quantiferon-CMV assays provided 46% concordance with the serology, 12% discordance, 18% disagreement between ELISPOT or Quantiferon-CMV and the serology, and 24% gray areas when one or both tests resulted in weak positives. None of the CMV-seronegative subjects showed detectable responses in the ELISPOT or the Quantiferon-CMV test. In transplant recipients, both the ELISPOT and Quantiferon-CMV assays positively correlated with each other and negatively correlated with CMV DNAemia in a significant way (P < 0.

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Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

et al. 2013

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“…Enzyme-linked immunosorbent spot (ELISPOT) and QuantiFERON (QFT) assays are the most standardized and employed platforms and were recently used to detect CMV-specific CMI in solid organ and allogeneic hematopoietic stem cell transplant recipients (27,28). Although their performances for CMV CMI were very similar, interassay differences were found (29,30).…”

Section: Maternal Cmv-specific T-cell Immunity As a Marker For Intraumentioning

confidence: 99%

Testing for Cytomegalovirus in Pregnancy

et al. 2017

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Congenital cytomegalovirus (CMV) infection represents a relevant cause of deafness and neurological damage in newborns. Intrauterine CMV transmission might result after primary or nonprimary infections, though at different rates (30% versus 0.2%, respectively). At present, a prenatal diagnosis of CMV infection is based mainly on maternal serology, the detection of CMV-DNA in amniotic fluid and fetal blood, and ultrasound (US) and magnetic resonance imaging (MRI). Recent evidences suggest that congenital CMV infection may be an immune-mediated disease and that evaluation of humoral and especially T-cell immunities may improve the overall prenatal diagnosis. This review summarizes the most recent advancements in the diagnosis of maternal and prenatal CMV infections.KEYWORDS human cytomegalovirus, laboratory assays, congenital infections, IgG avidity, CMV-ELISPOT, CMV-QuantiFERON, immunoserology, imaging T he human cytomegalovirus (CMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunocompromised patients and congenitally infected fetuses and newborns, resulting in a broad range of disabilities, including sensorineural hearing loss (SNHL), visual impairment, and motor and cognitive deficits. Other transient symptoms of congenital CMV infection (cCMV) may include hepatosplenomegaly, thrombocytopenia, and jaundice. The global prevalence of cCMV has been estimated at 0.7% (1), and fetal CMV transmission may arise from a maternal primary or nonprimary infection. The highest rate of cCMV occurs after primary infections in seronegative mothers (30 to 40%), while nonprimary infections, including CMV reactivations or reinfections, result in cCMV in 0.2 to 2% of cases, suggesting that preconceptional immunity may play a role in preventing intrauterine transmission (2). If the main burden of congenital infections in Europe and North America results from primary infections, then nonprimary infections represent the main cause of cCMV in developing countries or in poor socioeconomical contexts, since the seroprevalences among the resident populations are much higher (3). The severities of infections in neonates and infants are highly variable. It has been estimated that 10 to 15% of congenitally infected neonates are symptomatic at birth, and 40 to 58% of them will experience permanent long-term sequelae. Moreover, 13.5% of children with asymptomatic infections will develop late-onset sequelae, mainly consisting of hearing impairments and neurologic deficits. The effectiveness of antiviral treatment during pregnancy is still debated. Most of the concerns are related to the potential genotoxicity and teratogenicity of the drugs. The clinical benefits of CMV-specific hyperimmune globulin treatment are also disputed, due to discordant results obtained from different studies (4,5).In the last decade, major efforts have been made to improve the early laboratory diagnosis of maternal and fetal infections. Despite these efforts, at present, many countries in the world have not yet adopted a consolidate...

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“…ELISPOT assay results are expressed as the number of CMV pp65-specific IFN-␥ spotforming colonies (SFCs)/200,000 PBMCs. pp65 was chosen as a stimulus since it is considered to be among the major immunodominant antigens encoded by CMV (19,24,46) and has been widely used to detect CMVspecific T-cell responses in humans (1,2,7,23,41). In human trials, pp65 has also been shown to be a biologically relevant target to resolve and prevent clinically relevant infections (11,26).…”

Section: Methodsmentioning

confidence: 99%

Human Cytomegalovirus-Specific T-Cell Immune Reconstitution in Preemptively Treated Heart Transplant Recipients Identifies Subjects at Critical Risk for Infection

et al. 2012

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Human cytomegalovirus (CMV) infection represents a major threat for heart transplant recipients (HTXs). CMV-specific T cells effectively control virus infection, and thus, assessment of antiviral immune recovery may have clinical utility in identifying HTXs at risk of infection. In this study, 10 CMV-seropositive (R + ) pretransplant patients and 48 preemptively treated R + HTXs were examined before and after 100 days posttransplant. Preemptive treatment is supposed to favor the immune recovery. CMV DNAemia and gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay were employed to assess the viremia and immune reconstitution. HTXs could be categorized into three groups characterized by high (>100), medium (50 to 100), and low (<50) spot levels. Early-identified high responders efficiently controlled the infection and also maintained high immunity levels after 100 days after transplant. No episodes of grade ≥2R rejection occurred in the high responders. Midresponders were identified as a group with heterogeneous trends of immune reconstitution. Low responders were 41% and 21% of HTXs before and after 100 days posttransplant, respectively. Low responders were associated with a higher incidence of infection. The effect of viremia on immune recovery was investigated: a statistically significant inverse correlation between magnitude of viremia and immune recovery emerged; in particular, each 10-fold increase in viremia (>4 log 10 DNAemia/ml) was associated with a 36% decrease of the ELISPOT assay spot levels. All episodes of high viremia (>4 log 10 DNAemia/ml) occurred from 1 to 60 days after transplant. Thus, the concomitant evaluation of viremia and CMV immune reconstitution has clinical utility in identifying HTXs at risk of infection and may represent a helpful guide in making therapeutic choices.

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Diagnostic Utility of Human Cytomegalovirus-Specific T-Cell Response Monitoring in Predicting Viremia in Pediatric Allogeneic Stem-Cell Transplant Patients

Cited by 29 publications

References 51 publications

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

Comparison of Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot and CMV Quantiferon Gamma Interferon-Releasing Assays in Assessing Risk of CMV Infection in Kidney Transplant Recipients

Testing for Cytomegalovirus in Pregnancy

Human Cytomegalovirus-Specific T-Cell Immune Reconstitution in Preemptively Treated Heart Transplant Recipients Identifies Subjects at Critical Risk for Infection

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