title: 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.
abstract: 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 CMV-specific 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<0.05). During the antiviral prophylaxis, all 20 D+/R- KTRs we examined displayed undetectable Quantiferon-CMV and ELISPOT results, and there was no evidence of CMV seroconversion. The receiving operator curve (ROC) statistical analysis revealed similar specificities and sensitivities in predicting detectable viremia (areas under the curve [AUC], 0.66 and 0.62 for Quantiferon-CMV and ELISPOT, respectively). ELISPOT and Quantiferon-CMV values of >150 spots/200,000 peripheral blood mononuclear cells (PBMCs) and >1 to 6 IU gamma interferon (IFN-γ) were associated with protection from CMV infection (odds ratios [OR], 5 and 8.75, respectively). In transplant recipients, the two tests displayed similar abilities for predicting CMV infection. Both the ELISPOT and Quantiferon-CMV assays require several ameliorations to avoid false-negative results.
authors.affiliation: Department of Molecular Medicine, Padua General Hospital, University of Padua School of Medicine, Padua, Italy. davide.abate@unipd.it
authors.forename: Davide
authors.initials: D
authors.lastname: Abate
authors.forename: Alda
authors.initials: A
authors.lastname: Saldan
authors.forename: Carlo
authors.initials: C
authors.lastname: Mengoli
authors.forename: Marta
authors.initials: M
authors.lastname: Fiscon
authors.forename: Cristina
authors.initials: C
authors.lastname: Silvestre
authors.forename: Loredana
authors.initials: L
authors.lastname: Fallico
authors.forename: Marta
authors.initials: M
authors.lastname: Peracchi
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Furian
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cusinato
authors.forename: Luciana
authors.initials: L
authors.lastname: Bonfante
authors.forename: Barbara
authors.initials: B
authors.lastname: Rossi
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchini
authors.forename: Dino
authors.initials: D
authors.lastname: Sgarabotto
authors.forename: Paolo
authors.initials: P
authors.lastname: Rigotti
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
mesh_terms: D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D003951:Diagnostic Errors; D058501:Enzyme-Linked Immunospot Assay / Q000379:methods*; D005260:Female; D006801:Humans; D059425:Interferon-gamma Release Tests / Q000379:methods*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014180:Transplantation; D055815:Young Adult