RGD Reference Report - Integrative urinary peptidomics in renal transplantation identifies biomarkers for acute rejection. - Rat Genome Database

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Integrative urinary peptidomics in renal transplantation identifies biomarkers for acute rejection.

Authors: Ling, XB  Sigdel, TK  Lau, K  Ying, L  Lau, I  Schilling, J  Sarwal, MM 
Citation: Ling XB, etal., J Am Soc Nephrol. 2010 Apr;21(4):646-53. doi: 10.1681/ASN.2009080876. Epub 2010 Feb 11.
RGD ID: 7248773
Pubmed: PMID:20150539   (View Abstract at PubMed)
PMCID: PMC2844301   (View Article at PubMed Central)
DOI: DOI:10.1681/ASN.2009080876   (Journal Full-text)

Noninvasive methods to diagnose rejection of renal allografts are unavailable. Mass spectrometry followed by multiple-reaction monitoring provides a unique approach to identify disease-specific urine peptide biomarkers. Here, we performed urine peptidomic analysis of 70 unique samples from 50 renal transplant patients and 20 controls (n = 20), identifying a specific panel of 40 peptides for acute rejection (AR). Peptide sequencing revealed suggestive mechanisms of graft injury with roles for proteolytic degradation of uromodulin (UMOD) and several collagens, including COL1A2 and COL3A1. The 40-peptide panel discriminated AR in training (n = 46) and test (n = 24) sets (area under ROC curve >0.96). Integrative analysis of transcriptional signals from paired renal transplant biopsies, matched with the urine samples, revealed coordinated transcriptional changes for the corresponding genes in addition to dysregulation of extracellular matrix proteins in AR (MMP-7, SERPING1, and TIMP1). Quantitative PCR on an independent set of 34 transplant biopsies with and without AR validated coordinated changes in expression for the corresponding genes in rejection tissue. A six-gene biomarker panel (COL1A2, COL3A1, UMOD, MMP-7, SERPING1, TIMP1) classified AR with high specificity and sensitivity (area under ROC curve = 0.98). These data suggest that changes in collagen remodeling characterize AR and that detection of the corresponding proteolytic degradation products in urine provides a noninvasive diagnostic approach.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Transplant Rejection  IEP 7248773; 7248773mRNA:increased expression:kidneyRGD 
Transplant Rejection  ISOCOL1A2 (Homo sapiens)7248773; 7248773mRNA:increased expression:kidneyRGD 
Transplant Rejection  ISOCOL3A1 (Homo sapiens)7248773; 7248773mRNA:increased expression:kidneyRGD 

Objects Annotated

Genes (Rattus norvegicus)
Col1a2  (collagen type I alpha 2 chain)
Col3a1  (collagen type III alpha 1 chain)

Genes (Mus musculus)
Col1a2  (collagen, type I, alpha 2)
Col3a1  (collagen, type III, alpha 1)

Genes (Homo sapiens)
COL1A2  (collagen type I alpha 2 chain)
COL3A1  (collagen type III alpha 1 chain)


Additional Information