title: Molecular and Functional Noninvasive Immune Monitoring in the ESCAPE Study for Prediction of Subclinical Renal Allograft Rejection.
abstract: Subclinical acute rejection (sc-AR) is a main cause for functional decline and kidney graft loss and may only be assessed through surveillance biopsies.
  
  
  
  The predictive capacity of 2 novel noninvasive blood biomarkers, the transcriptional kidney Solid Organ Response Test (kSORT), and the IFN-γ enzyme-linked immunosorbent spot assay (ELISPOT) assay were assessed in the Evaluation of Sub-Clinical Acute rejection PrEdiction (ESCAPE) Study in 75 consecutive kidney transplants who received 6-month protocol biopsies. Both assays were run individually and in combination to optimize the use of these techniques to predict sc-AR risk.
  
  
  
  Subclinical acute rejection was observed in 22 (29.3%) patients (17 T cell-mediated subclinical rejection [sc-TCMR], 5 antibody-mediated subclinical rejection [sc-ABMR]), whereas 53 (70.7%) showed a noninjured, preserved (stable [STA]) parenchyma. High-risk (HR), low-risk, and indeterminate-risk kSORT scores were observed in 15 (20%), 50 (66.7%), and 10 (13.3%) patients, respectively. The ELISPOT assay was positive in 31 (41%) and negative in 44 (58.7%) patients. The kSORT assay showed high accuracy predicting sc-AR (specificity, 98%; positive predictive value 93%) (all sc-ABMR and 58% sc-TCMR showed HR-kSORT), whereas the ELISPOT showed high precision ruling out sc-TCMR (specificity = 70%, negative predictive value = 92.5%), but could not predict sc-ABMR, unlike kSORT. The predictive probabilities for sc-AR, sc-TCMR, and sc-ABMR were significantly higher when combining both biomarkers (area under the curve > 0.85, P < 0.001) and independently predicted the risk of 6-month sc-AR in a multivariate regression analysis.
  
  
  
  Combining a molecular and immune cell functional assay may help to identify HR patients for sc-AR, distinguishing between different driving alloimmune effector mechanisms.
authors.affiliation: 1 Laboratory of Nephrology, IDIBELL, Barcelona, Spain. 2 Division of Transplant Surgery, University of California, San Francisco, San Francisco, CA. 3 Kidney Transplant Unit, Bellvitge University Hospital, IDIBELL, UB, Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Crespo
authors.forename: Silke
authors.initials: S
authors.lastname: Roedder
authors.forename: Tara
authors.initials: T
authors.lastname: Sigdel
authors.forename: Szu-Chuan
authors.initials: SC
authors.lastname: Hsieh
authors.forename: Sergio
authors.initials: S
authors.lastname: Luque
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Cruzado
authors.forename: Tim Q
authors.initials: TQ
authors.lastname: Tran
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Grinyó
authors.forename: Minnie M
authors.initials: MM
authors.lastname: Sarwal
authors.forename: Oriol
authors.initials: O
authors.lastname: Bestard
mesh_terms: D000328:Adult; D000368:Aged; D064591:Allografts; D019540:Area Under Curve; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005819:Genetic Markers; D006084:Graft Rejection / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D013997:Time Factors; D014158:Transcription, Genetic; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; C573415:IFNG protein, human; D007371:Interferon-gamma