尘螨过敏儿童治疗的代谢组学与免疫调节协同机制研究

Eicosanoids, including Prostaglandins (PGs) and Leukotrienes (LTs) etc., are closely related to allergic asthma. However, it was hard to comprehensively analyze the eicosanoids by the structural diversity, high structural similarity and very low contents using previous metabolomics analytical approaches, therefore, it could not fully elucidate the pathogenesis and treatment mechanism of allergic diseases. Our previous studies showed that the analytical method based on derivatization-liquid chromatography-mass spectrometry (LC-MS)，which remarkably resolved above problems. The results indicated that the levels of eicosanoids for PGs and Hydroxyeicosatetraenoic acids (HETEs) in serum of dust mite allergic children were significantly higher than those in normal children, and the amounts of PGs and HETEs were significantly decreased after desensitization treatment, and related to the trend changes of sIgE lever to dust mites. It was definite that PGs and HETEs participated in the pathogenesis and treatment of allergic diseases. Thereafter we hypothesize that the mechanism of anti-inflammation, anti-oxidation and the formation of immune tolerance in allergic children coordinated regulated by eicosanoids metabolism and immunomodulation. In this study, series LC-MS approaches will be used to analyze the metabolome during desensitization in biofluids in dust mites-allergic children. In order to provide new biomarkers for the diagnosis and prognosis of allergic asthma, the regulation mechanism of dust mite sensitization and desensitization therapy was expounded in combination with the related indexes of immune antibody regulation.

类花生四烯酸(eicosanoids)，包括前列腺素类(PGs)和白三烯类(LTs)等与过敏性哮喘有密切关系。然而以往的代谢组学分析方法不能系统地研究种类繁多、结构类似和含量很低的eicosanoids，无法全面阐明过敏性疾病发病和治疗机理。我们前期研究显示，基于衍生化-液相色谱-质谱(LC-MS)分析方法发现尘螨过敏儿童血清eicosanoids中的PGs和羟基廿碳四烯酸类(HETEs)比正常儿童显着升高，通过脱敏治疗后两种代谢物显着降低，且与尘螨sIgE变化趋势相关，明确PGs和HETEs参与过敏性疾病发病机制，因此提出假设：eicosanoids代谢与免疫调节协同调控过敏患儿抗炎、抗氧化及形成免疫耐受。本研究将利用LC-MS联用技术，针对尘螨过敏患儿脱敏治疗中体液进行代谢组学分析，结合免疫抗体调节尘螨过敏和脱敏治疗的调控，为过敏性哮喘诊断和脱敏预后判断提供新的生物标志物。

花生四烯酸(eicosanoids)，包括前列腺素类(PGs)和白三烯类(LTs)等与过敏性哮喘有 密切关系。然而以往的代谢组学分析方法不能系统地研究种类繁多、结构类似和含量很低的ei cosanoids，无法全面阐明过敏性疾病发病和治疗机理。我们前期研究显示，基于衍生化-液相 色谱-质谱(LC-MS)分析方法发现尘螨过敏儿童血清eicosanoids中的PGs和羟基廿碳四烯酸类(H ETEs)比正常儿童显着升高，通过脱敏治疗后两种代谢物显着降低，且与尘螨sIgE变化趋势相 关，明确PGs和HETEs参与过敏性疾病发病机制，因此提出假设：eicosanoids代谢与免疫调节 协同调控过敏患儿抗炎、抗氧化及形成免疫耐受。本研究将利用LC-MS联用技术，针对尘螨过敏患儿脱敏治疗中体液进行代谢组学分析，结合免疫抗体调节尘螨过敏和脱敏治疗的调控，为过敏性哮喘诊断和脱敏预后判断提供新的生物标志物。