title: Effect of confounding factors on a phospho-flow assay of ribosomal S6 protein for therapeutic drug monitoring of the mTOR-inhibitor everolimus in heart transplanted patients.
abstract: BACKGROUND
  Several assays of monitoring immune cell function have been developed to enhance therapeutic drug monitoring.
  
  
  OBJECTIVE
  An in vitro-validated whole-blood assay of phosphorylated ribosomal protein S6 (pS6RP) was evaluated for confounders to monitor the mTOR-inhibitor everolimus (ERL).
  
  
  METHODS
  Whole blood samples from 87 heart transplant recipients were analyzed for pS6RP-expression in CD3-positive T-cells by phospho-flow analysis.
  
  
  RESULTS
  ERL blood concentration, laboratory parameters, co-medications, demographic and clinical data were reviewed.
  
  
  CONCLUSIONS
  Evaluating the pS6RP-assay revealed that pS6RP is influenced by cyclosporine A (CsA) blood concentration, duration of ERL treatment, co-medication with thiazide diuretics and different metabolic parameters.
authors.affiliation: a HELIOS Clinic, Department of Cardiac Surgery , University Hospital Leipzig, Heart Center , Leipzig , Germany.
authors.forename: Maja-Theresa
authors.initials: MT
authors.lastname: Dieterlen
authors.affiliation: a HELIOS Clinic, Department of Cardiac Surgery , University Hospital Leipzig, Heart Center , Leipzig , Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: John
authors.affiliation: a HELIOS Clinic, Department of Cardiac Surgery , University Hospital Leipzig, Heart Center , Leipzig , Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Haase
authors.affiliation: a HELIOS Clinic, Department of Cardiac Surgery , University Hospital Leipzig, Heart Center , Leipzig , Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Garbade
authors.affiliation: b HELIOS Clinic, Department of Pediatric Cardiology , University Hospital Leipzig, Heart Center , Leipzig , Germany.
authors.forename: Attila
authors.initials: A
authors.lastname: Tarnok
authors.affiliation: a HELIOS Clinic, Department of Cardiac Surgery , University Hospital Leipzig, Heart Center , Leipzig , Germany.
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Mohr
authors.affiliation: c Department of Cardiothoracic Transplantation and Advanced Cardiac Surgery , Florida Hospital Orlando , Orlando , FL , USA.
authors.forename: Hartmuth B
authors.initials: HB
authors.lastname: Bittner
authors.affiliation: d Department of Cardiovascular Surgery , University Heart Center Hamburg , Hamburg , Germany.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Barten
mesh_terms: D017252:CD3 Complex / Q000032:analysis; D016903:Drug Monitoring / Q000379:methods; D000068338:Everolimus / Q000097:blood*; D005434:Flow Cytometry / Q000379:methods; D016027:Heart Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D008875:Middle Aged; D010766:Phosphorylation; D038601:Ribosomal Protein S6 / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D017252:CD3 Complex; D007166:Immunosuppressive Agents; D038601:Ribosomal Protein S6; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: S6 ribosomal protein; everolimus; mTOR-inhibitor; phospho-flow