Primary Studies On Proteomic Fingerprints Of Renal Allograft Rejection By Seldi-Tof Ms

Objective To explore the serum proteomic fingerprints of renal allografl rejection,to screen biomarkers of the differently expressed proteins of the different groups of transplanted patients,to search non-invasive markers that would be useful and specific for early diagnosis.Methods Sera were collected from patients in acute clinical rejection group, in stable transplant group and in disease control(urinaemia).We used SELDI-TOF mass spectrometry(manufactured by Cipergen Biosystems Inc,Fermont,CA,USA) to compare protein profiles from sera of 3 defined patient groups.30 Samples from patients with acute clinical rejection(N＝5),50 from patients with stable transplant state(N-25),30 from patients with urinaemia(N＝15) as control were analyzed.The obtained spectra were subjected to bioinformatic analysis using BMW(Biomarker Wizard) and BPSS 5.0(Biomarker patterns systems).The classification decision tree (CDT) of clinical rejection were established.At last we gave a double-blind trial by using this diagnostic cast and analysis different stages of clinical rejection.Results In the range of m/z values 1000-100000,188 protein peaks were dectected which had statistical difference between three groups(p＜0.05) by the analysis of Biomarker Wizard Software,among which 51 had statistical predominant difference(p＜0.001).The biomarkers concentrated on molecular weight from 3888 to 5905,from 7344 to 9501,from 11342 to 11940 and from 12149 to 14687. 14 discriminatory protein peaks were up-regulated while 10 were down-regulated gradually,from disease control group to acute clinical rejection group to stable transplant group.We established the classification diagnostic tree of acute clinical rejection.2 protein peaks with m/z value of 8136,5872 distinguished different groups with sensitivity and specificity and positive predictive value of all 100%. Using this diagnostic cast,we gave a double-blind trial to another 55 serum samples and distinguished rejection stage from stable stage in acute clinical rejection group.Conclusions SELDI-TOF-MS could greatly facilitate discovery of biological markers of acute clinical rejection.The diagnostic pattern,which established by distinguished protein with high sensitivity and specificity and positive predictive value,could be useful to identify acute clinical rejection,and had clinical significance for treatment and precaution in the early stage.