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Title: Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection

Abstract

Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics using LC-MS/MS and ELISA to analyze a set of 92 urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundance of identified urinary proteins was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific urinary proteins in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (UMOD, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these urinary proteins in AR. This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of urinary proteins for serial, non-invasive clinical monitoring for graft rejection after

Authors:
; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
974939
Report Number(s):
PNNL-SA-68069
24698; 400412000; TRN: US201007%%898
DOE Contract Number:
AC05-76RL01830
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proteomics - Clinical Applications, 4(1):32-47; Journal Volume: 4; Journal Issue: 1
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; ABUNDANCE; ANTIGENS; DETECTION; DISEASES; ENZYME IMMUNOASSAY; MONITORING; PATIENTS; PROTEINS; SAMPLING; TRANSPLANTS; URINE; Environmental Molecular Sciences Laboratory

Citation Formats

Sigdel, Tara K., Kaushal, Amit, Gritsenko, Marina A., Norbeck, Angela D., Qian, Weijun, Xiao, Wenzhong, Camp, David G., Smith, Richard D., and Sarwal, Minnie M.. Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection. United States: N. p., 2010. Web. doi:10.1002/prca.200900124.
Sigdel, Tara K., Kaushal, Amit, Gritsenko, Marina A., Norbeck, Angela D., Qian, Weijun, Xiao, Wenzhong, Camp, David G., Smith, Richard D., & Sarwal, Minnie M.. Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection. United States. doi:10.1002/prca.200900124.
Sigdel, Tara K., Kaushal, Amit, Gritsenko, Marina A., Norbeck, Angela D., Qian, Weijun, Xiao, Wenzhong, Camp, David G., Smith, Richard D., and Sarwal, Minnie M.. Mon . "Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection". United States. doi:10.1002/prca.200900124.
@article{osti_974939,
title = {Shotgun Proteomics Identifies Proteins Specific for Acute Renal Transplant Rejection},
author = {Sigdel, Tara K. and Kaushal, Amit and Gritsenko, Marina A. and Norbeck, Angela D. and Qian, Weijun and Xiao, Wenzhong and Camp, David G. and Smith, Richard D. and Sarwal, Minnie M.},
abstractNote = {Acute rejection (AR) remains the primary risk factor for renal transplant outcome; development of non-invasive diagnostic biomarkers for AR is an unmet need. We used shotgun proteomics using LC-MS/MS and ELISA to analyze a set of 92 urine samples, from patients with AR, stable grafts (STA), proteinuria (NS), and healthy controls (HC). A total of 1446 urinary proteins were identified along with a number of NS specific, renal transplantation specific and AR specific proteins. Relative abundance of identified urinary proteins was measured by protein-level spectral counts adopting a weighted fold-change statistic, assigning increased weight for more frequently observed proteins. We have identified alterations in a number of specific urinary proteins in AR, primarily relating to MHC antigens, the complement cascade and extra-cellular matrix proteins. A subset of proteins (UMOD, SERPINF1 and CD44), have been further cross-validated by ELISA in an independent set of urine samples, for significant differences in the abundance of these urinary proteins in AR. This label-free, semi-quantitative approach for sampling the urinary proteome in normal and disease states provides a robust and sensitive method for detection of urinary proteins for serial, non-invasive clinical monitoring for graft rejection after},
doi = {10.1002/prca.200900124},
journal = {Proteomics - Clinical Applications, 4(1):32-47},
number = 1,
volume = 4,
place = {United States},
year = {Mon Jan 04 00:00:00 EST 2010},
month = {Mon Jan 04 00:00:00 EST 2010}
}