title: Diagnosis of subclinical and clinical acute T-cell-mediated rejection in renal transplant patients by urinary proteome analysis.
abstract: OBJECTIVE
  Noninvasive diagnosis of acute renal allograft rejection may be advantageous compared with the allograft biopsy.
  
  
  METHODS
  In this study, a multi-marker classification model for rejection was defined on a training set of 39 allograft patients by statistical comparison of capillary electrophoresis mass spectrometry (CE-MS) peptide spectra in urine samples from 16 cases with subclinical acute T-cell-mediated tubulointerstitial rejection and 23 nonrejection controls.
  
  
  RESULTS
  Application of the rejection model to a blinded validation set (n=64) resulted in an AUC value of 0.91 (95% CI: 0.82-0.97, p=0.0001). In total, 16 out of 18 subclinical and 10 out of 10 clinical rejections (BANFF grades Ia/Ib), and 28 out of 36 controls without rejection were correctly classified. Acute tubular injury in the biopsies or concomitant urinary tract infection did not interfere with CE-MS-based diagnosis. Sequence information of identified altered collagen α(I) and α (III) chain fragments in rejection samples suggested an involvement of matrix metalloproteinase-8 (MMP-8). Biopsy stainings revealed matrix metalloproteinase-8 exclusively in neutrophils located within peritubular capillaries and sparsely, in the tubulointerstitium during rejection.
  
  
  CONCLUSIONS
  The established marker set contains peptides related to tubulointerstitial infiltration seen in acute rejection. The set of urinary peptide markers will be used for early diagnosis of acute kidney allograft rejection marker in a multicenter phase III prospective study.
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany. metzger@mosaiques-diagnostics.com
authors.forename: Jochen
authors.initials: J
authors.lastname: Metzger
authors.forename: Christos
authors.initials: C
authors.lastname: Chatzikyrkou
authors.forename: Verena
authors.initials: V
authors.lastname: Broecker
authors.forename: Eric
authors.initials: E
authors.lastname: Schiffer
authors.forename: Lothar
authors.initials: L
authors.lastname: Jaensch
authors.forename: Alexander
authors.initials: A
authors.lastname: Iphoefer
authors.forename: Michael
authors.initials: M
authors.lastname: Mengel
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Wilfried
authors.initials: W
authors.lastname: Gwinner
mesh_terms: D000595:Amino Acid Sequence; D001185:Artificial Intelligence; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000652:urine*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000652:urine; D040901:Proteomics; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D010446:Peptide Fragments