Monitoring of CMV-specific cell-mediated immunity with a commercial ELISA-based interferon-γ release assay in kidney transplant recipients treated with antithymocyte globulin

Abstract

Monitoring for cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA-based interferon (IFN)-γ release assay (QTF-CMV) from posttransplant months 2-5 (362 points) in 120 CMVseropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty-seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF-CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF-CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV-CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1-year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P = .244). Specificity and PPV to predict protective CMV-CMI improved by elevating the IFN-γ cutoff value to 1.13 IU/mL (65.7% and 71.4%) and 7.0 IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF-CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG-treated CMV-seropositive KT recipients. This performance is slightly improved by modifying the IFN-γ positivity threshold.

Effects of Short-Term Corticosteroid Use on Reactogenicity and Immunogenicity of the First Dose of ChAdOx1 nCoV-19 Vaccine

“…IFN-γ was detected by ELISA and the measured optical density was converted to IFN-γ concentration (IU/mL) using ELISA Report Software (SD Biosensor). Because the positive cut-off value of the SARS-CoV-2 IGRA kit had not been established, IFN-γ concentration of the Sp tubes minus that of the Nil tube was compared quantitatively between the groups, and a tentative cut-off values were applied: mean + 3 standard deviations (SDs) of IFN-γ concentration of the Nil tubes (0.84 IU/mL), which is higher than that used in previous IGRAs for tuberculosis (0.35 IU/mL) or CMV (0.2 IU/mL) ( 14 , 15 ).…”

A Prospective Study of Cytomegalovirus-Specific Cell-Mediated Immune Monitoring and Cytomegalovirus Infection in Patients With Active Systemic Lupus Erythematosus Receiving Immunosuppressants

“…A previous study reported that the QuantiFERON-CMV assay before and 1 month after immunosuppression had suboptimal accuracy for predicting protective CMV-specific CMI (sensitivity, 77.4%; specificity, 34.3%; positive predictive value, 64.1%; and negative predictive value, 50.0%); there was a nonsignificant difference in 1-year CMV infection rates between QF− (nonreactive or indeterminate) and QF+ patients [ 33 ]. A few previous studies suggested a modified cutoff value (≥0.1 IU/mL) to increase the test’s sensitivity for immunocompromised patients, particularly CMV-seropositive SOT recipients [ 33 , 34 ]. We were able to distinguish those at risk of CMV infection by using the cutoff value suggested by the manufacturer 1 month postimmunosuppression.…”

Utility of CMV-Specific Immune Monitoring for the Management of CMV in Solid Organ Transplant Recipients: A Clinical Update

“…Not all studies have found a clear association between CMV-CMI and protection against future CMV infection. Recently, Fernandez-Ruiz et al reported on the assessment of CMV-CMI using QFN-CMV at EOP in R+ kidney transplant recipients receiving rATG induction [ 79 ]. Their data demonstrated suboptimal accuracy for predicting 1-year CMV infection rates (45.8% in persons with non-reactive or indeterminate results vs. 36.1% in persons with reactive results, p = 0.244).…”