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系统性自体免疫疾病

Systemic Autoimmune Diseases
课程网址: http://videolectures.net/promo_snezna_sodin_semrl_eng/  
主讲教师: Snežna Sodin-Šemrl
开课单位: 卢布尔雅那大学
开课时间: 2012-10-09
课程语种: 英语
中文简介:
我们在卢布尔雅那大学医学中心风湿病学系的研究小组由布拉罗兹曼教授于1974年至2010年领导。我们目前的研究项目“系统性自身免疫疾病”涵盖2个广泛领域,即疾病生物标志物,包括磷脂、微粒和血清淀粉样蛋白A的自身抗体,临床研究重点是了解致病机制和探索新疗法。基础研究领域包括用噬菌体文库测定抗β2糖蛋白I抗体的副位,利用表面等离子体共振鉴别高亲和力和低亲和力抗体,以及表征氧化修饰的免疫球蛋白对其结合能力和特异性的影响。我们领导了一项国际合作工作,以评估患者抗β2糖蛋白I抗体的亲和力,并开发了一种新的酶联免疫吸附试验(ELISA)以改进抗凝血酶原抗体检测,这两种方法都有助于优化对抗磷脂综合征的诊断。我们与Jo_ef Stefan研究所合作,利用原子力显微镜,报告了致病性抗膜联蛋白A5或抗β2糖蛋白I抗体是破坏磷脂表面保护膜联蛋白A5晶体屏障所必需的。与苏黎世大学的Steffen Gay教授一起,我们发现单核细胞衍生的微粒损害类风湿性关节炎滑膜成纤维细胞的凋亡,而microRNA-126则增加了凋亡。这代表了新的治疗目标。一项临床5年随访研究表明,抗β2糖蛋白I抗体与类风湿性关节炎患者动脉粥样硬化加速无关。另一项临床纵向研究表明,季节性和H1N1流感疫苗不仅有可能诱发罕见个体的短暂性,而且有可能诱发长期抗磷脂抗体的发展。我们将血清淀粉样蛋白A(SAA)的常规比浊法测量引入我们的诊断实验室,并与芝加哥西北大学的John Varga博士一起发现,SAA与系统性硬化症的肺受累相关,表明炎症和纤维化之间可能存在联系。首次在献血者体内发现抗SAA自身抗体,并建议其发挥生理调节作用。我们围绕SAA在炎症和感染方面的作用建立了一个15个国际合作伙伴联盟,并组织了一个为期3天的研讨会。迄今为止最重要的事件是2010年在卢布尔雅那召开的第七届国际自体免疫大会与耶胡达·肖恩菲尔德教授的联合组织。我们建立了一个生物药物注册中心,并参与了小儿抗磷脂综合征的注册。我们的团队也是一个由欧盟赞助的名为eumusc的项目的合作伙伴,该项目处理肌肉骨骼疾病。我们平均每年在SCI引用的期刊、书籍章节以及临床医生和患者指南上发表20篇论文。我们相信,我们的研究项目的优势在于临床、常规诊断和研究环境的连通性,我们计划在未来建立这些环境。
课程简介: Our research group within the Department of Rheumatology at the University Medical Center in Ljubljana has been led from 1974 to 2010 by Prof. Blaž Rozman. Our current research program entitled “Systemic Autoimmune Diseases” encompasses 2 broad areas, namely DISEASE BIOMARKERS including autoantibodies against phospholipids, microparticles and serum amyloid A and CLINICAL STUDIES focused on understanding the pathogenic mechanisms and exploring novel therapies. The basic research area includes determination of paratopes of anti-beta2 glycoprotein I antibodies with a phage library, differentiation of high and low avidity antibodies using surface plasmon resonance, as well as characterization of oxidatively modified immunoglobulin effects influencing their binding capacity and specificity. We have led an international collaborative effort in order to evaluate the avidity of anti-beta2 glycoprotein I antibodies in patients and developed a novel ELISA for improved anti-prothrombin antibody detection, both contributing to optimization of diagnostics for antiphospholipid syndrome. In collaboration with the Jožef Stefan Institute, using atomic force microscopy, we reported that pathogenic anti-annexin A5 or anti-beta2 glycoprotein I antibodies are necessary for the disruption of the protective annexin A5 crystalline shield over phospholipid surfaces. With Prof. Steffen Gay from the University of Zurich we showed that monocyte-derived microparticles impair apoptosis of rheumatoid arthritic synovial fibroblasts, while microRNA-126 increases it. This represents novel therapeutic targets. A clinical 5-year follow-up study demonstrated no involvement of anti-beta2 glycoprotein I antibodies in accelerated atherosclerosis of rheumatoid arthritic patients. Another clinical longitudinal study suggested that seasonal and H1N1 influenza vaccines have a potential to induce not only transient, but also long-term antiphospholipid antibody development in rare individuals. We introduced routine nephelometric measurement of serum amyloid A (SAA) into our diagnostic laboratory and with Dr. John Varga from Northwestern University, Chicago, we found that SAA was correlated with pulmonary involvement in systemic sclerosis indicating a possible link between inflammation and fibrosis. Anti-SAA autoantibodies were identified for the first time in blood donors and suggested to function as physiological regulators. We built a 15 partner international consortium around SAA’s roles in inflammation and infections, as well as organized a 3-day workshop. The most important event to date has been the co-organization of the 7th International Congress on Autoimmunity, 2010 in Ljubljana with Prof. Yehuda Shoenfeld. We developed a registry for Biological medications as well as participate in the registry for Pediatric-antiphospholipid syndrome. Our group is also a partner in an EU-sponsored project called EUMUSC, dealing with musculoskeletal disorders. On average, we publish 20 papers per year in SCI-cited journals, book chapters and guidelines for clinicians as well as patients. We believe the strengths of our research program lie within the connectivity of the clinical, routine diagnostic and research environments and we plan to build upon them in the future.
关 键 词: 医学; 全身性自身免疫病; 抗体
课程来源: 视频讲座网
最后编审: 2020-06-02:张荧(课程编辑志愿者)
阅读次数: 48