Electrochemical Immunosensing of ST2: A Checkpoint Target in Cancer Diseases

Rebeca M Torrente-Rodríguez,Pablo García De Frutos,Maria Gamella,José M Pingarrón,Neus Martínez-Bosch,Pilar Navarro,Susana Campuzano,María Pedrero,Cristina Muñoz-San Martín

doi:10.3390/bios11060202

Abstract

A magnetic beads (MB)-involved amperometric immunosensor for the determination of ST2, a member of the IL1 receptor family, is reported in this work. The method utilizes a sandwich immunoassay and disposable screen-printed carbon electrodes (SPCEs). Magnetic immunoconjugates built on the surface of carboxylic acid-microsized magnetic particles (HOOC-MBs) were used to selectively capture ST2. A biotinylated secondary antibody further conjugated with a streptavidin peroxidase conjugate (Strep-HRP) was used to accomplish the sandwiching of the target protein. The immune platform exhibits great selectivity and a low limit of detection (39.6 pg mL−1) for ST2, allowing the determination of soluble ST2 (sST2) in plasma samples from healthy individuals and patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) in only 45 min once the immunoconjugates have been prepared. The good correlation of the obtained results with those provided by an ELISA kit performed using the same immunoreagents demonstrates the potential of the developed strategy for early diagnosis and/or prognosis of the fatal PDAC disease.

Highlights

IL1RL1/IL33R encodes a member of the interleukin 1 receptor family known as ST2(or IL-33R), which consists of a transmembrane receptor (ST2L) and truncates solubleisoforms
It was reported that patients suffering from severity of metabolic syndrome (MetS), which comprises a group of metabolic abnormalities including central obesity, hypertension, diabetes mellitus (DM) or hyperglycaemia, high triglyceride (TG) levels, and low levels of high-density lipoprotein cholesterol (HDLC), showed high serum soluble ST2 (sST2) levels, regardless of sex and age [12]
Sandwich immunocomplexes labeled with HRP were prepared on the magnetic beads (MB) surface and amperometric transduction was performed, upon MBs magnetic capture on the surface of screen-printed carbon electrodes (SPCEs)

Summary

Introduction

IL1RL1/IL33R encodes a member of the interleukin 1 receptor family known as ST2(or IL-33R), which consists of a transmembrane receptor (ST2L) and truncates soluble (sST2)isoforms. ST2 has well-known relations with inflammatory diseases; elevated circulating levels of sST2 are found in the serum of patients suffering from several disorders such as systemic lupus erythematosus pulmonary fibrosis, rheumatoid arthritis, collagen vascular and asthma, as well as in inflammatory conditions including septic shock or trauma [1,2,3,4,5,6]. It was reported that patients suffering from severity of metabolic syndrome (MetS), which comprises a group of metabolic abnormalities including central obesity, hypertension, diabetes mellitus (DM) or hyperglycaemia, high triglyceride (TG) levels, and low levels of high-density lipoprotein cholesterol (HDLC), showed high serum sST2 levels, regardless of sex and age [12]. A study with chemotherapy-treated advanced pancreatic ductal adenocarcinoma (PDAC) patients showed that sST2-plasma levels lower than 13,064 pg mL–1 were related to higher overall survival (16 months) than those over the median (4 months) [19]. Increased levels of sST2 correlating with severity have been reported in plasma samples from patients with pancreatitis [20], a risk factor for PDAC initiation

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Conclusion