Differentially expressed serum proteins in children with or without asthma as determined using isobaric tags for relative and absolute quantitation proteomics

Abstract

Background Although asthma is one of the most common chronic, noncommunicable diseases worldwide, the pathogenesis of childhood asthma is not yet clear. Genetic factors and environmental factors may lead to airway immune-inflammation responses and an imbalance of airway nerve regulation. The aim of the present study was to determine which serum proteins are differentially expressed between children with or without asthma and to ascertain the potential roles that these differentially expressed proteins (DEPs) may play in the pathogenesis of childhood asthma. Methods Serum samples derived from four children with asthma and four children without asthma were collected. The DEPs were identified by using isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses. Using biological information technology, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Cluster of Orthologous Groups of Proteins (COG) databases and analyses, we determined the biological processes associated with these DEPs. Key protein glucose-6-phosphate dehydrogenase (G6PD) was verified by enzyme linked immunosorbent assay (ELISA). Results We found 46 DEPs in serum samples of children with asthma vs. children without asthma. Among these DEPs, 12 proteins were significantly (>1.5 fold change) upregulated and 34 proteins were downregulated. The results of GO analyses showed that the DEPs were mainly involved in binding, the immune system, or responding to stimuli or were part of a cellular anatomical entity. In the KEGG signaling pathway analysis, most of the downregulated DEPs were associated with cardiomyopathy, phagosomes, viral infections, and regulation of the actin cytoskeleton. The results of a COG analysis showed that the DEPs were primarily involved in signal transduction mechanisms and posttranslational modifications. These DEPs were associated with and may play important roles in the immune response, the inflammatory response, extracellular matrix degradation, and the nervous system. The downregulated of G6PD in the asthma group was confirmed using ELISA experiment. Conclusion After bioinformatics analyses, we found numerous DEPs that may play important roles in the pathogenesis of childhood asthma. Those proteins may be novel biomarkers of childhood asthma and may provide new clues for the early clinical diagnosis and treatment of childhood asthma.

Association between Glucose-6-Phosphate Dehydrogenase Deficiency and Asthma

“…In a study aimed at identifying differentially expressed proteins in the serum of children with and without asthma, G6PD was found to be significantly downregulated in asthmatic children [ 39 ], suggesting that enzyme deficiency may increase ROS, triggering kinase pathways that are able to facilitate viral replication and, in turn, aggravating airways injury. An additional study performed on a pediatric cohort using the microarray profiling technique identified the G6PD gene among the first three differentially expressed genes out of the 274 genes associated with asthma [ 40 ].…”

Screening differentially expressed proteins of coronary heart disease with congenital cold syndrome based on tandem mass tag (TMT) technology

“…For DEPs, Gene Ontology (GO) analysis ( http://geneontology.org/ ) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis ( https://www.kegg.jp/ ) and other specific bioinformatics analysis methods were used for further analysis as previously described [ 23 ]. GO annotation was used to analyze the DEPs categorized by biological process (BP), molecular function (MF), and cellular component (CC).…”

Current Insights on the Impact of Proteomics in Respiratory Allergies

“…This study identified 46 proteins differentially expressed, 12 up-regulated, and 34 down-regulated. These proteins were associated with the immune response, the inflammatory response, extracellular matrix degradation, and the nervous system [ 107 ]. Recently, in 2022, Weitoft and colleagues analyzed plasma samples after an allergen challenge by MS.…”

“…Immunoproteomics involves different techniques such as gels array-based techniques, MS, and in silico studies of their interactions with the immune system; the assessment of the allergens starts with allergen detection by serum from sensitized patients, followed by the characterization of the recognized proteins using MS. The MS has also been used to characterize natural extracts at pharmaceutical grade for allergen-specific immunotherapy [ 107 ] and monitor biomarkers in response to AIT. Using quantitative proteomics of pre-treatment sera derived from patients suffering from grass pollen allergy showed that high levels of O-glycosylated sialylated Fetuin-A isoforms correlated with a reduction of rhinoconjunctivitis symptoms after sublingual immunotherapy [ 108 ].…”