抗Jo-1抗体调控细胞间粘附分子（ICAM-1）在多发性肌炎/皮肌炎左室舒张功能不全的机制研究

心力衰竭是多发性肌炎/皮肌炎(PM/DM)最重要的死亡原因之一，但易被临床忽视。大约34.5%左右的PM/DM存在左室舒张功能不全（LVDD）,常发展为心力衰竭。PM/DM患者LVDD最重要的原因是心肌纤维化。据报道，抗Jo-1抗体是PM/DM最常见、最独特的抗体，可不依赖于其他炎症因子，单独调控细胞间粘附分子-1（ICAM-1）引起组织细胞纤维化。前期工作发现：PM/DM中LVDD患病率高达58%，与抗Jo-1抗体阴性PM/DM患者相比，阳性患者多项LVDD指标异常。因此，本课题拟以抗Jo-1抗体阳性PM/DM患者血清及纯化抗原刺激C57BL/6小鼠心肌细胞、构建PM/DM 小鼠模型及临床研究等方面探讨抗Jo-1抗体与ICAM-1、LVDD的相关性，阐明PM/DM患者LVDD的发病机制。此项目不仅对PM/DM合并LVDD的早期干预、降低死亡率有重要意义，还为药物干预治疗提供一条新的途径。

Heart failure (HF) constitutes a major cause of death in polymyositis /dermatomyositis (PM/DM). However, the clinical significance is not always attractive. Approximately 34.5% of patients with PM/DM had left ventricular diastolic dysfunction (LVDD), which often reslut in HF. Myocardial fibrosis is the most important cause of LVDD in PM/DM. It has been reported that anti-Jo-1 antibody , the most specific antibody, can regrelate intercellular adhesion molecule-1 leading to tissure fibrosis, independent of other cytokines. Our preliminary studies have confirmed the high prelacent of LVDD in PM/DM,and PM/DM with positive Jo-1 antibody had abnormal parameters of left ventricylar diastolic function compared with negative Jo-1 antibody patients. In the present study, we will 1) to investigate whether sera from positive anti-Jo-1 antibody patients or purified Jo-1 in PM/DM can activate intercellular adhesion molecule-1 in cardiac muscle cell; 2) to construct the murine model of Jo-1-mediated myositis and explore the pathogenesis of LVDD in PM/DM; 3) to assess the association among anti-Jo-1 antibody, ICAM-1 and LVDD in PM/DM patients. The study not only supplies important siginificance for early intervention and lowering mortality in PM/DM patients with LVDD, but also gives a novel method for drug intervention.