自身免疫性疾病治疗制剂的美国市场预测

人体免疫系统是一个复杂系统,它能极好地协调起来,攻击机体不欢迎的入侵者,癌症细胞或传染性疾病。但有时它会分不清敌友,攻击正常而健康组织,导致产生自身免疫性疾病,如类风湿性关节炎、系统性红斑狼疮、多发性硬化症或重症肌无力。     

靶定IL-17 治疗类风湿关节炎研究进展

IL-17作为前炎症因子参与类风湿关节炎,系统性红斑狼疮等自身免疫性疾病的病理过程。它主要由CD4+T细胞的一个亚群--Th17细胞分泌释放。目前,IL-17在类风湿关节炎的病理过程中的作用引起了医学界广泛的关注,抗IL-17A抗体已经生产并进入临床实验,用于治疗类风湿关节炎、银屑病关节炎等疾病。但其在类风湿关节炎病理过程中的作用尚需进一步研究,其有效性亦尚需进一步探讨。本文主要针对IL-17家族的各个亚型的表达、调控、生物学作用及与类风湿关节炎发病的关系进行阐述,为类风湿关节炎的治疗提供新的思路。     

风湿性疾病的药物治疗进展

风湿性疾病(风湿病)是以骨、关节、肌肉及关节周围软组织(肌腱、韧带、筋膜)为主要病变,具有疼痛和晨僵、慢性进展、畸形及破坏为特征的骨骼肌肉疾病。发病机制较为复杂,是遗传、性激素、环境因素、社会、生理、心理等因素相互作用下机体免疫功能紊乱而引起的慢性炎症性疾病。约有百余种,常见的有:(1)系统性红斑狼疮(SLE),干燥综合征,类风湿关节炎(RA),硬皮病,多发性肌炎/皮肌炎,系统性坏死性血管炎等弥漫性结缔组织病;(2)脊柱炎;(3)骨性关节炎及软组织疾病。治疗方法包括疾病教育、物理治疗、矫形、锻炼、药物和手术,其中以药物治疗为主…     

类风湿关节炎植物药治疗的研究进展

类风湿关节炎是一种以关节损害为主的最常见的自身免疫病.其有较高的致残及致畸率,严重危害人类健康,且DMARDs成为类风湿关节炎治疗的主流.而我国有丰富的植物药资源,近年来对于其在类风湿关节炎的治疗作用机制也成为研究的热点.主要的植物药有白芍总苷、雷公藤、青藤碱及羟基喜树碱.本文从体外研究、动物实验方面对其治疗机制进行分析与总结.     

白细胞介素-18在部分自身免疫性疾病中的作用

白细胞介素-18(interleukin-18,IL-18)是一个多肽片段,具有促进T细胞增殖、增强细胞毒性T细胞和自然杀伤细胞活性等功能。自身免疫性疾病是指机体对自身抗原发生免疫反应而导致自身组织损害所引起的疾病。IL-18在免疫调节中有着高效、广泛的作用,部分自身免疫性疾病发病与免疫系统的异常会伴随IL-18的高表达,且不同病程IL-18表达量会有规律性变化,因此IL-18可作为一种自身免疫性疾病较敏感的标志物。现对IL-18在常见自身免疫性疾病如系统性红斑狼疮、成人Still病、自身免疫性心肌炎和类风湿关节炎中的作用作一综述。     

治疗自身免疫性疾病的抗细胞因子疫苗

抗细胞因子疫苗是针对疾病相关细胞因子而设计与构建的一类能激发体液免疫应答的主动免疫治疗性疫苗,是用于自身免疫性疾病的一种极具潜力的新型疗法。目前研究与开发的抗细胞因子疫苗主要有2 种类型,一种是通过偶联载体或直接修饰为细胞因子引入外源表位而构建的蛋白疫苗,另一种则是可表达细胞因子免疫原的核酸疫苗。这两类疫苗在临床前及临床研究中,对各种自身免疫性疾病均显现出治疗活性。简介各类抗细胞因子疫苗及其作用机制,综述用于治疗类风湿性关节炎、多发性硬化症、系统性红斑狼疮等各种自身免疫性疾病的抗细胞因子疫苗研究进展。     

寄生虫治疗类风湿关节炎研究进展

在西方国家自身免疫性疾病的发病率增高,这可能是因为卫生条件改善,儿童时期感染的几率下降(卫生假说)。目前寄生虫感染是预防还是促进自身免疫性疾病还在讨论中。多种寄生虫用于不同的动物模型显示了其在多种疾病中限制疾病活动的能力,包括炎性肠病、多发硬化、1型糖尿病、类风湿关节炎和系统性红斑狼疮。目前大多数研究还在动物实验阶段,然而已经有一些临床试验在进行中。因此本文回顾了评估寄生虫的抗炎作用的几个临床试验及针对类风湿关节炎的动物实验。寄生虫诱导免疫调节的主要途径是抑制IFN-γ和IL-17产生,促进IL-4、IL-10和TGF-β释放,诱导CD4+T细胞Fox P3表达及调节性巨噬细胞细胞、树突状细胞和B细胞产生,然而寄生虫调节自身免疫性疾病的机制尚不完全清楚。目前寄生虫治疗类风湿关节炎在动物实验方面已经取得一定进展,进一步的研究是针对寄生虫调节免疫反应的有效成分模拟的人造类似物。     

利用cDNA-RDA技术研究BXSB狼疮小鼠差异表达的基因

利用近年来发展起来的代表性差异分析cDNA-RDA(cDNA-representational difference analysis)技术筛选BXSB红斑狼疮小鼠发病相关基因.发现了3个新的表达序列标签(EST)片段,在GenBank中的登录号分别为AF060113, AF060111, AF060110,同时发现了一些已知与自身免疫病相关的基因如逆转录病毒衣壳蛋白、Line-1逆转录酶等.通过RDA技术可能发现系统性红斑狼疮发病相关新基因,为自身免疫病的理论研究提供新的思路和方法.     

NETs在系统性红斑狼疮脑损伤机制中的研究进展

系统性红斑狼疮脑损伤(neuropsychiatric systemic lupus erythematosus, NPSLE)是自身免疫病系统性红斑狼疮累及神经系统发生损害后产生的严重并发症,多发于年轻女性,患病率极高,目前尚未找到有效的治疗方案。中性粒细胞胞外诱捕网(neutrophil extracellular traps, NETs)的形成和降解之间的稳态失衡,导致机体免疫功能紊乱,产生自身免疫性疾病。本文从血脑屏障、脑血管病变、血清和脑脊液、细胞因子、炎症反应的发生以及补体系统等方面对NPSLE的发病机制进行了总结,并进一步分析了NETs形成在NPSLE中的作用。     

雷公藤治疗类风湿关节炎

雷公藤有黄藤木、断肠草、蒸龙草、震龙根等别称,具有祛风除湿、活血通络、消肿止痛的作用。雷公藤作为治疗类风湿关节炎常用药的历史源远流长。类风湿关节炎(rheumatoid arthritis,RA)是一种自身免疫病,以侵蚀性关节炎为主要特征,其病理基础是滑膜炎,主要表现为关节肿胀和疼痛。本文先分别叙述雷公藤和类风湿,最后对近年来雷公藤治疗类风湿的临床研究和作用机制进行综述,以期为临床治疗RA的提供理论参考。     

Genetic susceptibility to autoimmune disorders: clues from gene association and gene expression studies

Susceptibility to autoimmune disorders results from the interaction of multiple genetic factors that regulate the threshold of autoreactivity. Genome-wide microsatellite screens and large-scale single nucleotide polymorphism (SNP) association studies have identified chromosomal loci that are associated with specific disorders including systemic lupus erythematosus, rheumatoid arthritis, juvenile arthritis, multiple sclerosis, and diabetes. Numerous candidate gene association studies have in turn investigated the association of specific genes within these chromosomal regions, with susceptibility to autoimmune diseases (e.g. FcgammaReceptors, TYK2 and systemic lupus). More recently, large-scale differential gene expression studies performed on selected tissues from patients with autoimmune disorders, have led to the identification of gene signatures associated with the activation of specific pathways in these diseases (e.g. interferon signature in lupus). In the future, integrated analyses of gene (and protein) expression together with SNP data will allow us to sketch an intelligible picture of the genesis of autoimmunity in humans. This review sets out to illustrate how the most recent advances in the field of systemic lupus erythematosus, rheumatoid arthritis and juvenile arthritis have led to a better understanding of these disorders.     

Type I interferon in organ-targeted autoimmune and inflammatory diseases

A significant role for IFNα in the pathogenesis of systemic lupus erythematosus is well supported, and clinical trials of anti-IFNα monoclonal antibodies are in progress in this disease. In other autoimmune diseases characterized by substantial inflammation and tissue destruction, the role of type I interferons is less clear. Gene expression analysis of peripheral blood cells from patients with rheumatoid arthritis and multiple sclerosis demonstrate an interferon signature similar to but less intense than that seen in patients with lupus. In both of those diseases, presence of the interferon signature has been associated with more significant clinical manifestations. At the same time, evidence supports an anti-inflammatory and beneficial role of IFNβ locally in the joints of patients with rheumatoid arthritis and in murine arthritis models, and many patients with multiple sclerosis show a clinical response to recombinant IFNβ. As can also be proposed for type I diabetes mellitus, type I interferon appears to contribute to the development of autoimmunity and disease progression in multiple autoimmune diseases, while maintaining some capacity to control established disease - particularly at local sites of inflammation. Recent studies in both rheumatoid arthritis and multiple sclerosis suggest that quantification of type I interferon activity or target gene expression might be informative in predicting responses to distinct classes of therapeutic agents.     

Autophagy in immunity: Implications in etiology of autoimmune/autoinflammatory diseases

Autophagy is now emerging as a spotlight in trafficking events that activate innate and adaptive immunity. It facilitates innate pathogen detection and antigen presentation, as well as pathogen clearance and lymphocyte homeostasis. In this review, we first summarize new insights into its functions in immunity, which underlie its associations with autoimmunity. As some lines of evidence are emerging to support its role in autoimmune and autoinflammatory diseases, we further discuss whether and how it affects autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus and multiple sclerosis, as well as autoinflammatory diseases, such as Crohn disease and vitiligo.     

Toll-like receptors in rheumatic diseases: Are we paying a high price for our defense against bugs?

In the last decade Toll-like receptor (TLR) research has led to new insights in the pathogenesis of many rheumatic diseases. In autoimmune diseases like systemic lupus erythematosus, rheumatoid arthritis and systemic sclerosis TLR signaling is likely to be involved in tolerance breakthrough and chronic inflammation via combined Fc gamma receptors and TLR recognition of immune complexes. Furthermore, inflammatory diseases like psoriatic arthritis and gout also show more and more evidence for TLR involvement. In this review we will discuss the involvement of TLR signaling in several rheumatic diseases and stress their similarities and differences based on recent findings.     

Autophagy in immunity

Autophagy is now emerging as a spotlight in trafficking events that activate innate and adaptive immunity. It facilitates innate pathogen detection and antigen presentation, as well as pathogen clearance and lymphocyte homeostasis. In this review, we first summarize new insights into its functions in immunity, which underlie its associations with autoimmunity. As some lines of evidence are emerging to support its role in autoimmune and autoinflammatory diseases, we further discuss whether and how it affects autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus and multiple sclerosis, as well as autoinflammatory diseases, such as Crohn disease and vitiligo.     

Autoantibody profiling for the study and treatment of autoimmune disease

Proteomics technologies enable profiling of autoantibody responses using biological fluids derived from patients with autoimmune disease. They provide a powerful tool to characterize autoreactive B-cell responses in diseases including rheumatoid arthritis, multiple sclerosis, autoimmune diabetes, and systemic lupus erythematosus. Autoantibody profiling may serve purposes including classification of individual patients and subsets of patients based on their 'autoantibody fingerprint', examination of epitope spreading and antibody isotype usage, discovery and characterization of candidate autoantigens, and tailoring antigen-specific therapy. In the coming decades, proteomics technologies will broaden our understanding of the underlying mechanisms of and will further our ability to diagnose, prognosticate and treat autoimmune disease.     

Past,present and future drug treatment for rheumatoid arthritis and systemic lupus erythematosus

Historically, treatment of complex autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus has aimed to relieve symptoms, and in severe cases, use broad-spectrum immunosuppressive treatments in attempts to induce permanent remission. Recent research into the causes of chronic autoimmune inflammatory activation have not only explored the mechanism of action of known therapies, but also provided a number of new targets for therapy, by identifying the cells, cytokines and signalling pathways activated during autoimmune antibody mediated processes. This review briefly outlines progress in the understanding of the autoimmune nature of rheumatoid diseases and the expansion of treatment options, from broad to specific immunotherapies for these closely related diseases.     

The use of patient-specific stem cells in different autoimmune diseases

Autoimmune diseases are developed when the immune system mistakenly attacks the body’s cells. These inflammatory disorders can be inherited or triggered by external forces, such as type 1 diabetes, which is caused by the immune system's destruction of pancreatic beta cells. So far, stem cells such as hESC and iPSC have been used to treat autoimmune disorders such as type 1 diabetes, rheumatoid arthritis (RA), multiple sclerosis (MS), and systemic lupus erythematosus (SLE), although these procedures have certain ethical concerns. On the other hand, bone marrow-derived mesenchymal stem cells (BM-MSC) are thought to be the best source of stem cells. Later, it was shown that mesenchymal stem cells produced from autologous adipose tissues have a great potential for producing huge volumes of stem cells. In-vitro and in-vivo investigations using autologous hematopoietic stem cells and autologous mesenchymal stem cells have been carried out on various rodent and human models, while clinical trials for inflammatory diseases such as multiple sclerosis and diabetes mellitus have yielded promising results. We attempted to summarise the usage of diverse stem cells in the therapy of various autoimmune disorders in this review. Shortly, we expect that the use of autologous stem cells will provide a new perspective on the treatment of autoimmune disorders.