RESUMO
Background: Allergic rhinitis (AR) is one of the most common clinical allergic diseases. Early diagnosis and medical intervention will benefit patients with allergic rhinitis. In this study, we focused on changes in urine proteomics in AR patients to investigate their potential clinical utility in AR diagnosis and evaluation. Material and methods: TMT-labeled mass spectrometry-based proteomics was carried out to identify differentially expressed proteins (DEPs) in urine between allergic rhinitis patients and normal control groups. The molecular biological role of DEPs was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) network analysis. Results: Enrichment analysis showed that the differentially expressed proteins were mainly related to cell-cell adhesion, complement and coagulation cascades, peptidase activity regulation, MAP kinase activity, etc. Compared with the NC group, HLA-DRB1, WFDC12, and DEFA4, among the top ten up-regulated proteins in the urine of the AR group, were related to the biological process of the humoral immune response. Among the top 10 down-regulated proteins, GUSB, SQSTM1, and KIT are related to protein domain-specific binding in terms of molecular function. Conclusions: We found differential protein changes between AR patients and normal subjects may be related to the pathophysiological changes of AR, which provides the possibility for further exploration of urinary proteomics biomarkers in the future.
RESUMO
BACKGROUND: There are limitations in detecting methods for early diagnosis and screening of allergic rhinitis. Considering the anti-inflammatory and anti-oxidative effects of bilirubin, this study aims to explore the relationship between bilirubin and allergic rhinitis and to identify bilirubin-related candidate urinary protein biomarkers associated with allergic rhinitis. METHODS: 63 allergic rhinitis patients (AR group) and 86 healthy controls (NC group) were enrolled. Venous blood was obtained to measure serum total IgE levels and bilirubin parameters. Patients in the AR group were then classified into the AR1 group (IgE > 125 IU/mL) and the AR2 group (IgE ≤ 125 IU/mL). After randomly selecting ten urine samples from the AR1 group, ten samples were chosen from the AR2 and the NC groups, respectively, according to age and gender matching. We employed a Tandem Mass Tag-Based liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) proteomics approach and targeted parallel-reaction monitoring(PRM) to identify and validate urinary biomarkers for allergic rhinitis. RESULTS: Compared with the NC group, the bilirubin levels of the AR group, AR1 group, and AR2 group were significantly lower. Although the bilirubin level of the AR1 group was lower than that of the AR2 group, the difference was not significant. Further urinary proteomics analysis found that the expression levels of proteins related to bilirubin metabolism and transportation in the AR1 and AR2 groups, including ABCC1, GSTA1, GSTO1, GSTM3, GSTM5, and BLVRB, were significantly higher than those in the NC group. By PRM-based quantification, GSTA1 and GSTO1 showed significant differences in different degrees of Allergic Rhinitis groups and healthy controls. The AUC of the combined diagnosis of GSTA1 and GSTO1 was 0.79 (95% CI 0.583-0.997, P = 0.007), and the sensitivity and specificity were 100% and 60.0%, respectively. CONCLUSIONS: Bilirubin levels are associated with allergic rhinitis. Our study revealed that urine proteomics has a specific value for exploring the pathophysiological mechanism of bilirubin changes in AR patients and screening possible biomarkers.