title: Monitoring of intracellular adenosine triphosphate in CD4(+) T cells to predict the occurrence of cytomegalovirus disease in kidney transplant recipients.
abstract: The measurement of intracellular concentrations of adenosine triphosphate (iATP) in phytohemagglutinin-stimulated CD4(+) T cells constitutes a surrogate marker for post-transplant cell-mediated immunity (CMI). This assay has shown suboptimal accuracy for predicting infection after kidney transplantation (KT). We hypothesize that its predictive capacity depends on the specific contribution of the CMI to host-pathogen interactions. We assessed iATP levels in 100 KT recipients at baseline and months 1, 3, and 6 (363 measurements). No association was found between iATP at month 1 and the risk for overall or bacterial infection, although such association was evident for cytomegalovirus (CMV) disease (multivariate-adjusted hazard ratio [per 50-unit increment]: 0.83; P-value = 0.048). There were no significant differences in mean iATP between stable patients (319.4 ng/ml) and those developing overall (304.1 ng/ml) or bacterial infection (346.9 ng/ml) over the 45 days following monitoring. However, iATP was significantly lower in patients who developed CMV disease (223.5 ng/ml; P-values <0.002). The optimal cutoff (265 ng/ml) for predicting CMV disease in patients not receiving antiviral prophylaxis yielded sensitivity, specificity, positive, and negative predictive values of 85.7%, 68.3%, 15.2%, and 98.6%, respectively. In conclusion, a non-pathogen-specific monitoring of CMI by means of iATP informs the risk of CMV disease in KT recipients.
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: María Asunción
authors.initials: MA
authors.lastname: Pérez-Jacoiste Asín
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain. mario_fdezruiz@yahoo.es.
authors.forename: Mario
authors.initials: M
authors.lastname: Fernández-Ruiz
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: López-Medrano
authors.affiliation: Department of Immunology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Aquilino
authors.affiliation: Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: González
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Tamara
authors.initials: T
authors.lastname: Ruiz-Merlo
authors.affiliation: Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutiérrez
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: San Juan
authors.affiliation: Department of Immunology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Estela
authors.initials: E
authors.lastname: Paz-Artal
authors.affiliation: Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Amado
authors.initials: A
authors.lastname: Andrés
authors.affiliation: Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (i+12), School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: José Maria
authors.initials: JM
authors.lastname: Aguado
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007107:Immune System; D007111:Immunity, Cellular; D007166:Immunosuppressive Agents; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D051437:Renal Insufficiency / Q000150:complications / Q000601:surgery*; D012306:Risk; D066027:Transplant Recipients
chemical_list: D007166:Immunosuppressive Agents; D000255:Adenosine Triphosphate
keywords: ImmuKnow assay; cytomegalovirus disease; immune monitoring; intracellular adenosine triphosphate; kidney transplantation; predictive value