title: Usefulness of immune monitoring in lung transplantation using adenosine triphosphate production in activated lymphocytes.
abstract: BACKGROUND
  The ImmuKnow (Cylex Inc, Columbia, MD) assay measures the amount of adenosine triphosphate (ATP) produced by helper CD4(+) cells after stimulation with a T-cell mitogen. We hypothesized that this assay can be used to assess the immune function of lung transplant recipients and identify those at risk of developing acute cellular rejection and respiratory infection.
  
  
  METHODS
  Lung transplant recipients at University of California Los Angeles between January 1, 2006 and December 31, 2009 received a bronchoscopy with broncheoalveolar lavage, transbronchial biopsy and ImmuKnow values drawn at regular intervals as well as during episodes of clinical deterioration. The recipient's clinical condition at each time-point was classified as healthy, acute cellular rejection, or respiratory infection. Mixed-effects models were used to compare the ATP levels among these groups, and odds ratios for rejection and infection were calculated.
  
  
  RESULTS
  The mean ATP level was 431 ± 189 ng/ml for the rejection group vs 377 ± 187 ng/ml for the healthy group (p = 0.10). A recipient with an ATP level > 525 ng/ml was 2.1 times more likely to have acute cellular rejection (95% confidence interval [CI] 1.1-3.8). Similarly, the mean ATP level was 323 ± 169 ng/ml for the infection group vs 377 ± 187 ng/ml for the healthy group (p = 0.03). A recipient with an ATP level < 225 ng/ml was 1.9 times more likely to have respiratory infection (95% CI, 1.1-3.3). However, the test was associated with poor performance characteristics. It had low sensitivity, specificity with an area under the receiver operating characteristic curve of only 0.61 to diagnose rejection and 0.59 to diagnose infection.
  
  
  CONCLUSIONS
  The ImmuKnow assay appears to have some ability to assess the overall immune function of lung transplant recipients. However, this study does not support its use as a reliable predictor of episodes of acute cellular rejection or respiratory infection.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095-1690, USA. mshino@mednet.ucla.edu
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Shino
authors.forename: S Samuel
authors.initials: SS
authors.lastname: Weigt
authors.forename: Rajan
authors.initials: R
authors.lastname: Saggar
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Ariss
authors.initials: A
authors.lastname: Derhovanessian
authors.forename: Aric L
authors.initials: AL
authors.lastname: Gregson
authors.forename: Rajeev
authors.initials: R
authors.lastname: Saggar
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Kubak
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Lynch
authors.forename: John A
authors.initials: JA
authors.lastname: Belperio
authors.forename: Abbas
authors.initials: A
authors.lastname: Ardehali
authors.forename: David J
authors.initials: DJ
authors.lastname: Ross
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D000255:Adenosine Triphosphate