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Comparative Proteomic Research In The Serum Of Allergic Rhinitis Cases

Posted on:2013-02-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y X LvFull Text:PDF
GTID:1114330374487843Subject:Otorhinolaryngology
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Charpter1The study of serum proteomics and bioinformatics analysis on perennial allergic rhinitisObjective Allergic rhinitis (AR) is a very common disease and a great risk factor for allergic asthma. Allergen specific immunotherapy is a promising method for changingthe course of allergic rhinitis progression. However, the exact mechanisms of the pathogenesis of allergic rhinitis and the specific immunotherapy have not been fully elucidated. The purposes of this study are to identify the regulatory networks active in perennial allergic rhinitis patients and those receiving specific immunotherapy and then to explore the functions of these regulatory networks. Finally, provide the foundation for the further mechanisms of allergic rhinitis and the specific immunotherapy.Methods45perennial allergic rhinitis patients,22SIT-effective and20SIT-ineffective allergic rhinitis patients and20healthy controls were recruited for this study. Isobaric tags for relative and absolute quantitation followed by two-dimensional gel electrophoresis and mass spectrometry were used to identify proteins that were differentially expressed among the four groups. The proteins that were significantly differentially expressed were clustered using EXPANDER v5.1software. The regulatory network pathways were identified, and the proteins associated with specific immunotherapy treatment were put into these pathways using Metacore software.Results A total number of210differential expressed proteins were identified, of which188were significantly associated with allergic rhinitis and91were closely asscociated with allergen specific immunotherapy. Using Metacore pathway software to build10regulatory pathway with the p-value in which the blood coagulation pathway received the smallest P value. The proteins including coagulation factor â…©â…¡, coagulation factor â…¢, F2, alpha-2-macroglobulin and plasminogen of blood coagulation pathway were changed between allergic rhinitis patients, specific immunotherapy-ineffective patients and specific imm- unotherapy-effective patients. In allergic rhinitis group its expression was increased,and in the allergic rhinitis group after specific immunotherapy, the expression of it was decreased in specific immunotherapy effective group and in the specific immunetherapy ineffective group its expression was elevated or did not change significantly. In this study, we also used Metacore software to build the network of transcription factors, the STAT3and STAT1transcription factor network may be closely related to the activation of the coagulation pathways with the highest correlation oefficient.Conclusion The blood coagulation pathway which consist coagulation factor â…©â…¡ coagulation factor â…¢, prothrombin, alpha-2macroglobulin and plasminogen may be an important regulator of the inflammatory response in allergic rhinitis. Specific immunotherapy may reduce the allergic inflammation by inhibiting the activation of coagulation pathways to improve the symptoms of allergic rhinitis. And the coagulation pathway may be acted through STAT3and/or STAT1transcription factor network to regulate the pathogenesis of AR and the activation of the specific immunotherapy. Charpter2Identication of the expression of Thrombin in serum Allergic Rhinitis patientsObjective Allergic rhinitis is a nasal inflammatory disorders with a high prevalence. The mechanism of the disease has been always in hot discussion, but remains unclear to date. The first chapter have confirmed that the activation and/or inhibition of the blood coagulation pathway might be plays an important roles in the mechanism of inflammatory response of allergic rhinitis and in the efficacy of specific immunotherapy for allergic rhinitis. And in this study we choose the central protein thrombin as the object, detected the expression of it in the surum of allergic rhinitis and specific immunotherapy patients. And try to explore the significance of the thrombin in allergic rhinitis and in specific immunotherapy patients; and then to investigate the correlation of the blood coagulation pathways and allergic rhinitis and the specific immunotherapyMethods The serum levels thrombin were measured by using enzyme immunoassay in patients with allergic rhinitis (n=20), specific immunotherapy effective patients (n=20) and specific immunotherapy ineffective patients (n=20) compared with those in healthy controls (n=20).Results Significantly different serum levels of Thrombin were observed among the control group and three patient groups, respectively. Inter-group analysis shows that in patients with allergic rhinitis the expression of thrombin was higher than in controls (P<0.001). And in allergen specific immunotherapy effective patients the expression was lower than allergic rhinitis patients (P<0.001). There was also siginificant difference between allergen specific immunotherapy effective patients and the allergen specific immunotherapy ineffective patients(P<0.001).Conclusion Thrombin may contribute to the development of allergic rhinitis. Further validated from the point level the coagulation pathway is closely related to allergic rhinitis. The periodic inspect the change of thrombin content in patients with allergic rhinitis may be able to predict the effect of specific immunotherapy and determine the termination time of specific immunotherapy. However, there might be different mechanism underling allergic rhinitis and the allergen specific immunotherapy, for which further studies are still necessary.
Keywords/Search Tags:Allergic Rhinitis, Perennial, Proteomics, iTRAQ, Networks, Thrombin
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