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CHARACTERIZATION OF RENAL ALLOGRAFT REJECTION BY SERUM PROTEOMIC ANALYSIS.
Qiuheng Zhang Ph.D 1, H. Albin Gritsch M.D. 2 and Elaine F. Reed Ph.D 1. 1 UCLA Immunogenetics Center, Department of Pathology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA and 2 Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA .
Proteomic-based identification of disease biomarkers is gaining attention in organ transplantation because of its potential application to diagnosis of graft rejection and dysfunction. We used SELDI mass spectrometry (Ciphergen) methods to analyze the serum proteome in renal transplant patients with biopsy-proven acute rejection and compared these results to transplant recipients with stable graft function. Forty-eight sera samples from 8 renal transplant recipients with acute rejection and 8 patients without rejection were analyzed by SELDI mass spectrometry. Replicate serum samples were denatured with urea and detergent and applied to 4 different protein chip arrays: anion exchange, cation exchange, reverse phase and metal affinity. Arrays were read at different laser intensities to detect both high and low mass proteins and peak data were imported into Ciphergen Express for analysis. Candidate spectra were identified by their molecular weight and ranked by their ability to distinguish nonrejection versus rejection based on receiver operating characteristic (ROC) curve (AUC). Sera from patients with stable functioning grafts were significantly different from patients with rejection by proteins at molecular masses of 11.5kDa,(p < 0.001), 11.7 kDa (p < 0.001) and 123.5 kDa (p < 0.01). In conclusion, proteome analysis of sera from transplant recipients may become a useful tool for noninvasive monitoring of renal allografts.