Shotgun proteomics identifies proteins specific for acute renal transplant rejection

Tara K. Sigdel, Amit Kaushal, Marina Gritsenko, Angela D. Norbeck, Wei-Jun Qian, Wenzhong Xiao, David G. Camp, Richard D. Smith, Minnie M. Sarwal
2010 PROTEOMICS - Clinical Applications  
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 applying LC-MS/MS and ELISA to analyze a set of 92urine 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
more » ... 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 kidney transplantation.
doi:10.1002/prca.200900124 pmid:20543976 pmcid:PMC2883247 fatcat:t4e3l6q5zvfhroujmkq3lenq5a