title: Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study.
abstract: BACKGROUND
  Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease.
  
  
  METHODS
  We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease.
  
  
  RESULTS
  Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively.
  
  
  CONCLUSIONS
  This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis.
  
  
  BACKGROUND
  NCT00817908.
authors.affiliation: Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Switzerland. oriol.manuel@chuv.ch
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
authors.forename: Deepali
authors.initials: D
authors.lastname: Kumar
authors.forename: Carlos
authors.initials: C
authors.lastname: Zayas
authors.forename: Steve
authors.initials: S
authors.lastname: Mawhorter
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Levi
authors.forename: Jayant
authors.initials: J
authors.lastname: Kalpoe
authors.forename: Luiz
authors.initials: L
authors.lastname: Lisboa
authors.forename: Leticia
authors.initials: L
authors.lastname: Ely
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Kaul
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: Michele I
authors.initials: MI
authors.lastname: Morris
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ison
authors.forename: Belinda
authors.initials: B
authors.lastname: Yen-Lieberman
authors.forename: Anthony
authors.initials: A
authors.lastname: Sebastian
authors.forename: Maha
authors.initials: M
authors.lastname: Assi
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D018890:Chemoprevention / Q000379:methods; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000009:adverse effects; D059425:Interferon-gamma Release Tests; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D018570:Risk Assessment; D019737:Transplants / Q000009:adverse effects*
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents