细胞因子缺陷在恶性血液病并肺部念珠菌感染的内在机制研究

The mortality rate is as high as 45% in the patient with hematological malignancies complicated with invasive fungal infection (IFI).The impaired immune function may increase the incidence of IFI. Although immunosuppressive state existed in all the patients with malignant hematologic disease, but the genetic susceptibility is different between the individuals. Our previous studies found that the level of cytokines were significant different between different individuals in acute leukemia, however, this effect of the individual difference on IFI is not clear. It is known that the cytokine participates in antifungal immunity process. Therefore, the expression of genes related to immune and cytokines will be studied in patients with hematological malignancies complicated with pulmonary Candida infection. The gene sequencing will be detected by using Sequenom mass spectrometry, and the genetic susceptibility to the immune related gene polymorphism will be analyzed in the patients with hematological malignancies complicated with pulmonary Candida infection. .To explore the intrinsic mechanism of the genes related to immune and cytokines in pulmonary Candida infection ,the relation between the expression of the immune related genes and cytokines will be detected by the peripheral blood mononuclear cells stimulated with Candida. The study will contribute to the realization of risk stratification to predict IFI in patients with hematologic malignancies.

恶性血液病并发侵袭性真菌感染(IFI)病死率高达45%。各种原因所造成免疫功能受损，均会增加IFI的发生率。恶性血液病患者均存在免疫抑制状态，但个体间遗传易感性差异极大。前期研究发现急性白血病不同的个体之间细胞因子水平存在显著差异，然而这种个体间差异对IFI的影响尚不清楚。鉴于细胞因子参与机体抗真菌免疫过程，本课题首先研究恶性血液病并肺部念珠菌感染患者免疫相关基因及细胞因子表达水平；采用Sequenom 质谱检测法分析免疫相关基因多态性与恶性血液病并肺部念珠菌感染患者的遗传易感性的关系；采用外周血单核细胞刺激试验检测样本免疫相关基因与细胞因子表达的关系，探索肺部念珠菌感染中免疫相关基因及细胞因子表达的路径对该疾病发生的可能内在机制，为实现恶性血液病患者发生IFI危险性的分层预测提供可能。