title: Derivation and validation of a cytokine-based assay to screen for acute rejection in renal transplant recipients.
abstract: OBJECTIVE
  Acute rejection remains a problem in renal transplantation. This study sought to determine the utility of a noninvasive cytokine assay in screening of acute rejection.
  
  
  METHODS
  In this observational cross-sectional study, 64 patients from two centers were recruited upon admission for allograft biopsy to investigate acute graft dysfunction. Blood was collected before biopsy and assayed for a panel of 21 cytokines secreted by PBMCs. Patients were classified as acute rejectors or nonrejectors according to a classification rule derived from an initial set of 32 patients (training cohort) and subsequently validated in the remaining patients (validation cohort).
  
  
  RESULTS
  Although six cytokines (IL-1β, IL-6, TNF-α, IL-4, GM-CSF, and monocyte chemoattractant protein-1) distinguished acute rejectors in the training cohort, logistic regression modeling identified a single cytokine, IL-6, as the best predictor. In the validation cohort, IL-6 was consistently the most accurate cytokine (area under the receiver-operating characteristic curve, 0.85; P=0.006), whereas the application of a prespecified cutoff level, as determined from the training cohort, resulted in a sensitivity and specificity of 92% and 63%, respectively. Secondary analyses revealed a strong association between IL-6 levels and acute rejection after multivariate adjustment for clinical characteristics (P<0.001).
  
  
  CONCLUSIONS
  In this pilot study, the measurement of a single cytokine can exclude acute rejection with a sensitivity of 92% in renal transplant recipients presenting with acute graft dysfunction. Prospective studies are needed to determine the utility of this simple assay, particularly for low-risk or remote patients.
authors.affiliation: Schuster Family Transplantation Research Center, Renal Division, Brigham and Women's Hospital & Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sacha A
authors.initials: SA
authors.lastname: De Serres
authors.forename: Bechara G
authors.initials: BG
authors.lastname: Mfarrej
authors.forename: Monica
authors.initials: M
authors.lastname: Grafals
authors.forename: Leonardo V
authors.initials: LV
authors.lastname: Riella
authors.forename: Ciara N
authors.initials: CN
authors.lastname: Magee
authors.forename: Melissa Y
authors.initials: MY
authors.lastname: Yeung
authors.forename: Christine
authors.initials: C
authors.lastname: Dyer
authors.forename: Usaila
authors.initials: U
authors.lastname: Ahmad
authors.forename: Anil
authors.initials: A
authors.lastname: Chandraker
authors.forename: Nader
authors.initials: N
authors.lastname: Najafian
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001900:Boston; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508598:IL4 protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor