Plasma peptidome profiling of acute hepatitis E patients by MALDI-TOF/TOF

Abstract

BackgroundHepatitis E is endemic to resource-poor regions, where it manifests as sporadic cases and large waterborne outbreaks. The disease severity ranges from acute self-limited hepatitis with low mortality to fulminant hepatic failure with high mortality. It is believed that the host response plays an important role in determining the progression and outcome of this disease. We profiled the plasma peptidome from hepatitis E patients to discover suitable biomarkers and understand disease pathogenesis.ResultsThe peptidome (< 10 kDa) fraction of plasma was enriched and analyzed by mass spectrometry. A comparative analysis of the peptide pattern of hepatitis E patients versus healthy controls was performed using ClinPro Tools. We generated a peptide profile that could be used for selective identification of hepatitis E cases. We have identified five potential biomarker peaks with m/z values of 9288.6, 7763.6, 4961.5, 1060.572 and 2365.139 that can be used to reliably differentiate between hepatitis E patients and controls with areas under the receiver operating characteristic curve (AUROC) values of 1.00, 0.954, 0.989, 0.960 and 0.829 respectively. A number of proteins involved in innate immunity were identified to be differentially present in the plasma of patients compared to healthy controls.ConclusionsBesides the utility of this approach for biomarker discovery, identification of changes in endogenous peptides in hepatitis E patient plasma has increased our understanding of disease pathogenesis. We have identified peptides in plasma that can reliably distinguish hepatitis E patients from healthy controls. Results from this and an earlier proteomics study are discussed.

Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

“…Taneja et al (25) studied the plasma protein profi le in patients with hepatitis E. In that study, the levels of complement proteins C3, C3f, C4, and bradykinin and kininogen were found to be lower in the plasma of hepatitis E patients compared to healthy controls. Any perturbation, such as a viral infection in the liver, should trigger a strong innate response as the fi rst line of host defense, but the opposite was found to occur, with these proteins being in downregulation.…”

Detection of Leishmania donovani infection using magnetic beads-based serum peptide profiling by MALDI-TOF MS in mice model

“…Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis of peptide or protein profiling in biological fluids has become a new potential tool for the diagnosis of human disease, due to its speed, ease of use, and accuracy (Fiedler et al 2007;Mantini et al 2010;Taneja et al 2011;Xiao et al 2011). The objective of this study was to assess the feasibility of serum peptide profiling used to detect Leishmania donovani infection in mice using MALDI-TOF MS.…”

Establishment and application of a high-quality comparative analysis strategy for the discovery and small-scale validation of low-abundance biomarker peptides in serum based on an optimized novel peptide extraction method

“…Some of the LMW biomarkers discovered using these methods are indicative of disease onset [1][2][3][4][5][6][7] , suggesting that native peptides may represent an unexplored archive of histological information. However, only a small proportion of peptides present in serum/plasma at concentrations above 100 ng/mL can be analyzed using conventional approaches.…”

“…Serum/plasma contains thousands of different types of proteins and peptides [1][2][3][4][5] and can provide valuable information about the numerous processes that take place within the body. Quantitative analysis of the proteins/peptides in serum/plasma samples is frequently employed in research aimed at discovering disease-specific biomarkers useful for the early detection of disease, for predicting drug susceptibility, and for evaluating prognosis [6][7][8][9] .…”