Proteomic profiling of renal allograft rejection in serum using magnetic bead–based sample fractionation and MALDI-TOF MS

Abstract

Proteomics is one of the emerging techniques for biomarker discovery. Biomarkers can be used for early noninvasive diagnosis and prognosis of diseases and treatment efficacy evaluation. In the present study, the well-established research systems of ClinProt Micro solution incorporated unique magnetic bead sample preparation technology, which, based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), have become very successful in bioinformatics due to its outstanding performance and reproducibility for discovery disease-related biomarker. We collected fasting blood samples from patients with biopsy-confirmed acute renal allograft rejection (n = 12), chronic rejection (n = 12), stable graft function (n = 12) and also from healthy volunteers (n = 13) to study serum peptidome patterns. Specimens were purified with magnetic bead-based weak cation exchange chromatography and analyzed with a MALDI-TOF mass spectrometer. The results indicated that 18 differential peptide peaks were selected as potential biomarkers of acute renal allograft rejection, and 6 differential peptide peaks were selected as potential biomarkers of chronic rejection. A Quick Classifier Algorithm was used to set up the classification models for acute and chronic renal allograft rejection. The algorithm models recognize 82.64% of acute rejection and 98.96% of chronic rejection episodes, respectively. We were able to identify serum protein fingerprints in small sample sizes of recipients with renal allograft rejection and establish the models for diagnosis of renal allograft rejection. This preliminary study demonstrated that proteomics is an emerging tool for early diagnosis of renal allograft rejection and helps us to better understand the pathogenesis of disease process.

The Big Drink Debate: perceptions of the impact of price on alcohol consumption from a large scale cross-sectional convenience survey in north west England

“…Conversely, tax cuts, which reduced the price of alcohol in Finland, were associated with increased alcohol-related mortality [11]. However, despite this, the price of alcohol continues to decline in real terms in many European countries [12,13]. …”

Proteomics in Transplantation

“…Subsequent construction of transcription regulation networks identified NF-κB, STAT1, and STAT3 as key transcription regulators in acute rejection [36]. Further small-scaled clinical proteomic studies detected serum peptide fingerprints that distinguish acute and chronic rejection [37] and acute rejection from acute tubular necrosis [38]. Just recently, Cibrik et al identified a plasma protein signature of 17 protein biomarkers for patients with acute renal allograft rejection.…”

Biomarker Characterization by MALDI–TOF/MS

“…Since biomolecular profiling will reflect changes in developmental, physiological, and pathological processes [178][179][180][181][182][183][184][185], several approaches have used bimolecular profiling for valid clinical diagnoses. Multivariate analysis such as principal component analysis (PCA) is often involved in these approaches to efficiently identify differences in biomolecular patterns between samples [186,187].…”