A prospective, proteomics study identified potential biomarkers of encapsulating peritoneal sclerosis in peritoneal effluent

Abstract

Encapsulating peritoneal sclerosis (EPS) is a potentially devastating complication of peritoneal dialysis (PD). Diagnosis is often delayed due to the lack of effective and accurate diagnostic tools. We therefore examined peritoneal effluent for potential biomarkers that could predict or confirm the diagnosis of EPS and would be valuable in stratifying at-risk patients and driving appropriate interventions. Using prospectively collected samples from the Global Fluid Study and a cohort of Greek PD patients, we utilized 2D SDSPAGE/ MS and iTRAQ to identify changes in the peritoneal effluent proteome from patients diagnosed with EPS and controls matched for treatment exposure. We employed a combinatorial peptide ligand library to compress the dynamic range of protein concentrations to aid identification of low-abundance proteins. In patients with stable membrane function, fibrinogen γ-chain and heparan sulphate proteoglycan core protein progressively increased over time on PD. In patients who developed EPS, collagen-α1(I), γ-actin and Complement factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HS-glycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and α1-antitrypsin were decreased compared to controls. Dynamic range compression resulted in an increased number of proteins detected with improved resolution of protein spots, compared to the full fluid proteome. Intelectin-1, dermatopontin, gelsolin, and retinol binding protein-4 were elevated in proteome-mined samples from patients with EPS compared to patients that had just commenced peritoneal dialysis. Thus, prospective analysis of peritoneal effluent uncovered proteins indicative of inflammatory and pro-fibrotic injury worthy of further evaluation as diagnostic/prognostic markers.

The Complement System in Dialysis: A Forgotten Story?

“…The study by Oliveira et al found strong protein abundance of Factor D in six adult PD patients ( 81 ), whereas a similar approach in 76 PD patients by Wen et al found significant protein expression of C4 and C3 only ( 82 ). Altogether, proteomic analyses of the dialysate of healthy PD patients has revealed the presence of C4, C3, Factor B, Factor D, Factor H, Factor I, and C9 ( 81 – 85 ). Proteomic profiling in the peritoneal fluid of children identified a total number of 189 proteins, of which 18 complement components ( 84 ).…”

“…The bioincompatibility of these solutions presumably promotes the expression TGF-b, thereby stimulating the transition of mesothelial cells to myofibroblasts. Recently, a prospective proteomics study identified complement components as a possible biomarker of encapsulating peritoneal sclerosis ( 85 ). Factors B and factor I were elevated in the PD fluid of patients up to 5 years prior to developing encapsulating peritoneal sclerosis.…”

The Human In Vivo Biomolecule Corona onto PEGylated Liposomes: A Proof‐of‐Concept Clinical Study

“…Strikingly, the most abundant corona protein (full‐length cDNA clone, CS0DD006YL02), which contributed to 8% of the total protein content, was not detected in any of the plasma control samples (Figure C; Table S4, Supporting Information). Although, full‐length cDNA clone CS0DD006YL02 has been previously identified by mass spectrometry analysis of arachnoid cyst fluid, peritoneal effluent and saliva, current proteomic approaches fail to detect this low‐abundance protein in complex mixtures like plasma.…”

Effects of Alanyl-Glutamine Treatment on the Peritoneal Dialysis Effluent Proteome Reveal Pathomechanism-Associated Molecular Signatures

“…Nevertheless, previous proteomic efforts to develop novel PDE biomarkers have been hindered by the PDE's plasma-like dynamic range of protein abundances, by the limited performance of separation and detection techniques applied to date, and by the design of the clinical trials from which the PDE samples were obtained. Thirteen published proteomic analyses of soluble PDE proteins have to date identified 171 unique proteins ( 7 – 19 ).…”