IgA肾病(IgAN)是我国最常见的原发性肾小球疾病，其发病机理尚未完全清楚。本实验室已完成的IgAN全基因组关联分析提示α-防御素单核苷酸多态性与IgAN显著相关，α-防御素可能参与IgAN的发生(Nature Genetics,2011)。项目组前期从mRNA和蛋白质表达水平分析发现IgAN患者外周血、尿液和肾组织中α-防御素某些类型的表达水平显著升高；表面等离子共振结果显示α-防御素能与异常糖基化IgA1结合，但其动力学与正常对照来源的IgA1差异显著。为进一步阐明α-防御素与疾病的关系，我们拟探讨其与异常糖基化IgA1相互作用的模型与机制，通过体外实验研究其对肾小球系膜细胞的影响和效应机制，如α-防御素和α-防御素-异常糖基化IgA1对细胞增殖、外基质形成及细胞因子表达的作用效应和信号调控机制。通过上述研究，旨在阐明α-防御素在IgAN发生中的作用及机理，为疾病治疗提供新的思路。

IgA nephropathy (IgAN) is the most common form of idiopathic glomerulonephritis (GN) in China. However，the exact pathogenic mechanism of IgAN remains unclear. The result published on "Nature Genetics" from our lab showed that single nucleotide polymorphrism of α-defensin gene DEFAs (rs2738048) was significantly related with IgAN, and α-defensin gene maybe a susceptibility gene for IgAN in Chinese Han patients. In order to characterize the expression pattern of α-defensin in IgAN patients, we plan to detect all types of α-defensins expression level in serum, urine and renal tissues of IgA nephropathy patients and normal control by ELISA,real-time PCR and immunofluorescence. Our previous results revealed that HNP1-4 was significantly increased in serum and renal tissue of IgAN patients, but no change in urine. It is reported that some types of α-defensins (HNP1-4 and HD5) have lectin-like activity. Whether α-defensins have ability to bind galactosylated IgA1 or not, and if it done, what are their roles in IgAN pathogenesis? In order to answer these questions, we have isolated IgA1 from serum of IgAN patients and normal control by affinity purification and gal filtration, and applied surface plasmon resonance (SPR) techniques to gain insights into this property. The results of SPR revealed that α-defesin (HNP1-3) have affinity to bind galactosylated IgA1 from IgAN patients or from normal control in a concentration-dependent manner, while the kinetics of interaction were significantly different. Based on these, we plan to further study the interaction pattern and mechanism of α-defensin with galactosylated IgA1, and make clearly the mechanisms of α-defensin and/or α-defensin-galactosylated IgA1 interaction on cell proliferation, collagen, Fn and cytokines production in human glomerular mesangial cells, hoping to find their potential roles as new therapeutic targets or biomarkers. In brief, we hope that this research will shed some new light on the mechanism study of IgAN pathogenesis and offer new strategies for the clinical treatment.