title: Identification of T Cell-Mediated Vascular Rejection After Kidney Transplantation by the Combined Measurement of 5 Specific MicroRNAs in Blood.
abstract: BACKGROUND
  MicroRNAs (miRNAs, miR) hold important roles in the posttranscriptional regulation of gene expression. Their function has been correlated with kidney disease, and they might represent a new class of biomarkers for frequent evaluation of renal graft status. We analyzed their potential in identifying severe T cell-mediated vascular rejection (TCMVR) (Banff 4-II/III) in kidney transplanted patients.
  
  
  METHODS
  Microarray experiments and semiquantitative real-time reverse transcription polymerase chain reaction were performed with total RNA isolated from blood cells of kidney graft recipients. Initial microarray analysis revealed 23 differentially expressed miRNAs distinguishing patients with TCMVR from patients with stable grafts. From these, we validated and further determined the expression of 6 differentially expressed miRNAs and 2 control miRNAs in 161 samples from patients with T cell-mediated rejection (Banff 3-Borderline, Banff 4-I/II/III), Banff-2 antibody-mediated rejection, Banff-5 interstitial fibrosis/tubular atrophy, in samples from stable patients and in samples from patients with urinary tract infection using real-time reverse transcription polymerase chain reaction.
  
  
  RESULTS
  Expression levels of all 6 candidate miRNAs were significantly downregulated in blood of TCMVR patients compared to the other groups and displayed high sensitivities and specificities for diagnosing TCMVR. The combination of 5 miRNAs, identified by an unbiased multivariate logistic regression followed by cross-validation, enhanced the sensitivity and specificity for the diagnosis of TCMVR after renal transplantation.
  
  
  CONCLUSIONS
  The combined measurement of miRNA-15B, miRNA-16, miRNA-103A, miRNA-106A, and miRNA-107 may help to better identify TCMVR after renal transplantation in a precise and clinically applicable way.
authors.affiliation: 1 Department of Nephrology, Universitätsmedizin Charité Campus Mitte, Berlin, Germany. 2 Deutsches Rheuma-Forschungszentrum, Charitéplatz, Berlin, Germany. 3 Department of Pathology, Universitätsmedizin Charité, Campus Mitte, Berlin, Germany. 4 Labor Berlin GmbH, Berlin, Germany. 5 Medical Immunology Department, Universitätsmedizin Charité, Campus Virchow, Berlin, Germany. 6 Institute for Transfusion Medicine and HLA Typing Laboratory, Universitätsmedizin Charité, Campus Virchow, Klinikum, Berlin, Germany.
authors.forename: Mareen
authors.initials: M
authors.lastname: Matz
authors.forename: Katharina
authors.initials: K
authors.lastname: Fabritius
authors.forename: Christine
authors.initials: C
authors.lastname: Lorkowski
authors.forename: Michael
authors.initials: M
authors.lastname: Dürr
authors.forename: Jens
authors.initials: J
authors.lastname: Gaedeke
authors.forename: Pawel
authors.initials: P
authors.lastname: Durek
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Grün
authors.forename: Anne
authors.initials: A
authors.lastname: Goestemeyer
authors.forename: Friederike
authors.initials: F
authors.lastname: Bachmann
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Wu
authors.forename: Birgit
authors.initials: B
authors.lastname: Rudolph
authors.forename: Danilo
authors.initials: D
authors.lastname: Schmidt
authors.forename: Ulrike
authors.initials: U
authors.lastname: Weber
authors.forename: Claudia
authors.initials: C
authors.lastname: Haftmann
authors.forename: Nadine
authors.initials: N
authors.lastname: Unterwalder
authors.forename: Nils
authors.initials: N
authors.lastname: Lachmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Hans-H
authors.initials: HH
authors.lastname: Neumayer
authors.forename: Mir-Farzin
authors.initials: MF
authors.lastname: Mashreghi
authors.forename: Klemens
authors.initials: K
authors.lastname: Budde
mesh_terms: D019540:Area Under Curve; D016000:Cluster Analysis; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D005819:Genetic Markers; D006084:Graft Rejection / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D016030:Kidney Transplantation / Q000009:adverse effects*; D016015:Logistic Models; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics*; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; C544749:MIRN103 microRNA, human; C542541:MIRN106 microRNA, human; C549045:MIRN107 microRNA, human; C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs