Screening And Identification Of Serum Related Differential Proteins In Patients With Chronic Urticaria By Proteomic Techniques

【Objective】To analyze the differentially expressed proteins in peripheral blood of CU patients by comparing the basic clinical data of chronic urticaria(CU)patients with high or low clinical symptom scores and healthy controls,to search for the functional and metabolic pathways of differentially expressed proteins,and to preliminarily explore the possible pathogenesis of chronic urticaria from the perspective of proteomics.【Methods】1.Thirty-three CU patients and 12 healthy controls were included according to the diagnostic criteria of Chinese Clinical Dermatology.CU patients were divided into 15 patients with high CU score and 18 patients with low CU score according to the urticaria activity scale(UAS).The basic clinical data among three groups and the blood lipid levels between high CU score group and low CU score group were compared,and the dermoscopic data of the patients with skin lesions were collected.2.Proteomic analysis of 45 serum samples from patients with chronic urticaria(33cases)and healthy controls(12 cases)was carried out using TMT and LC-MS/MS to obtain the original proteomic data3.Mascot 2.2 and Proteome Discoverer 1.4 software were used to identify and quantify the proteins collected from the original data,and the differential proteins among the three groups were screened out.4.All differentially expressed proteins identified were bioinformatically analyzed using cluster analysis,GO functional enrichment analysis,KEGG pathway enrichment analysis and protein interaction network analysis,and further screened for statistically significant proteins and pathways related to the pathogenesis of chronic urticaria.5.Data processing is carried out by SPSS 22.0 statistical software and Excel software.Variance analysis was used for comparison of quantitative variables and multiple means;t test was used for sample mean comparison,expressed as mean(+standard deviation);and chi-square test was used for enumeration data.P <0.05 was considered statistically significant.【Results】1.Total cholesterol(TCHOL),triglycerides(TG),high-density lipoprotein C(HDL-C)and low-density lipoprotein C(LDL-C)in patients with high CU score were not significantly different from those with low CU score(P < 0.05).2.Local or systemic wheal in CU patients showed typical dermoscopic characteristics,including light pink background and linear branched vascular network.3.831 proteins were detected in the blood samples of high CU score group,low CU score group and healthy control group by proteomic analysis.The 831 proteins detected were screened for differentially expressed proteins with fold change greater than 1.2 fold(up-regulation greater than 1.2 times or down-regulation less than 0.83)and P value less than 0.05.Compared with healthy control group,there were 6 up-regulated proteins and 10 down-regulated proteins in high CU score group.Compared with the healthy control group,there were there were 5up-regulated proteins and 6 down-regulated protein in the low CU score group.Compared with the low CU score group,there were 5 up-regulated protein and 5down-regulated protein,of which the down-regulated ferritin light chain was 0.72,P=0.01.4.The differentially expressed proteins in high CU score group,low CU score group and healthy control group were enriched by GO function analysis.The differentially expressed proteins are mainly involved in biological processes such as blood coagulation and fibrin clot formation,innate immune response,and activation of signal transduction.The KEGG pathway enrichment analysis maps to important pathways such as complement and coagulation cascade,platelet activation;5.Compared with the healthy control group,the CU score high group and the CU score low group had common differentially expressed proteins between the two control groups,and the up-regulation of the expression included intercellular adhesion molecule 3,and the expression down-regulation included fibrinogen alpha chain、fibrinogen beta chain、fibrinogen gamma chain、insulin-like growth factor I.At the same time,the protein network analysis showed that fibrinogen alpha chain、fibrinogen gamma chain、insulin-like growth factor I、fibrinogen beta chain and other differentially expressed proteins have a high degree of connectivity,which were 10,8,8 and 6,respectively.【Conclusion】1.TCHOL,TG,HDL-C and LDL-C had no significant statistical difference between patients with high CU score and low CU score.2.Proteomic results showed that there were many protein molecular changes in blood samples of high CU score group,low CU score group and healthy control group.A total of 831 proteins were identified.ferritin light chain may be one of the parameters for eveluating the severity of clinical symptoms of chronic urticaria.3.The results of KEGG pathway enrichment analysis showed that complement and coagulation cascade and platelet activation may play a role in the pathogenesis of chronic urticaria.4.Differentially expressed protein cluster analysis and interaction network analysis,in which the differential expression of protein fibrinogen may play a key role in some aspects of the development of chronic urticaria.