title: Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels: prediction of acute rejection vs. viral replication events.
abstract: Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.
authors.affiliation: Division of Pediatric Nephrology, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA. vikasmd@peds.ufl.edu
authors.forename: Vikas R
authors.initials: VR
authors.lastname: Dharnidharka
authors.forename: Sushil
authors.initials: S
authors.lastname: Gupta
authors.forename: Eihab
authors.initials: E
authors.lastname: Al Khasawneh
authors.forename: Allah
authors.initials: A
authors.lastname: Haafiz
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Theriaque
authors.forename: Amir H
authors.initials: AH
authors.lastname: Shahlaee
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Garrett
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002648:Child; D005260:Female; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods*; D011446:Prospective Studies; D012306:Risk; D014184:Transplantation, Homologous / Q000379:methods; D016896:Treatment Outcome; D014779:Virus Replication
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000255:Adenosine Triphosphate