PTX3在类风湿关节炎的骨免疫发病机制中的作用研究

正五聚蛋白3（Pentraxin-related protein, PTX3)是一种由381种氨基酸构成的长链正五聚蛋白。在调控促炎信号、参与炎症反应和维持免疫自稳中起到重要作用。项目申请人所在团队利用蛋白质组学等高通量技术，在RA相关新型生物标志物的研究中鉴定：PTX3对RA疾病诊断具有较高的特异性（74.9%），尤其对ACPA阴性RA患者也达到了74.4%，具有重要临床意义，极具应用前景。但目前关于PTX3和anti-PTX3参与RA骨免疫发病机制中的作用尚不明确。本项目拟探讨异常表达的PTX3对于RA的T/B淋巴细胞和单核细胞的异常活化及功能中起到的作用，以及PTX3对于RA关节局部滑膜细胞的增值、炎症及骨破坏的作用机制。通过体外实验，明确PTX3在RA发病免疫炎症和破骨两个方面的调控作用，以明确其参与RA发病的骨免疫机制，为研发新的免疫干预靶点提供依据。

Pentraxin-related protein(PTX3) is a long pentraxin with 381 amino acids, which belongs to the pentraxin family.PTX3 is produced in response to pro inflammatory signals and regulates inflammatory responses and autoimmunity.In our previous study of detecting biomarkers using proteomics technology, PTX3 is a novel biological marker of RA. The specificity of PTX3 in the diagnosis of RA is 74.9% and, in ACPA negative RA patients, the specificity is as high as 74.4%, indicating the remarkable clinical value.Our study has shown that PTX3 is highly expressed in serum. However, whether PTX3 and anti-PTX3 antibodies involve in the pathogenesis of RA is still unknown. We designed a series of studies to verify the hypothesis. In this study, we would explore the role of PTX3 in the proliferation and inflammation of FLS, the regulation of PTX3 in T/B lymphocytes. Overall, we would identify the regulation function of PTX3 in osteoimmunity in RA.This novel role of PTX3 in RA might help better understand the pathogenesis and the identification of new target of treatment.