世界自身免疫疾病和狼疮治疗药物研究开发最新进展

类风湿性关节炎,多发性硬化,1型糖尿病和狼疮都是自身免疫疾病。这样的命名是因为免疫系统错误地把人体自己的蛋白质作为外来的入侵者识别,并开始产生攻击健康细胞和组织的抗体。估计     

系统性红斑狼疮和其他自身免疫病治疗药研发进展

系统性红斑狼疮（SLE）和其他自身免疫病的治疗／治愈问题一直困扰着医药学界。过去近40年没有一个新治疗药获得批准，不过现时在研发中的一些药物可能会有希望。然而，一家独立的市场分析公司Datamonitor的一篇最新报告提到，由于对临床试验要求存在分歧，阻碍了这些药物获准的机会，但这并不防碍医生超标签范围使用这些药物。     

世界自身免疫疾病和狼疮治疗药物研究开发最新进展

类风湿性关节炎，多发性硬化，1型糖尿病和狼疮都是自身免疫疾病。这样的命名是因为免疫系统错误地把人体自己的蛋白质作为外来的入侵者识别，并开始产生攻击健康细胞和组织的抗体。估计遭受自身免疫疾病的5000万美国人的75％是妇女。妇女患上自身免疫疾病比男人高三倍。为什么？一种理论解释说：妇女比男人具有增强的免疫系统，这增强了妇女对许多类型的感染的抵抗力，但也更易受自身免疫疾病的影响。     

自身免疫异常疾病及其治疗新途径

人体正常的免疫系统由于某种原因而出现免疫功能紊乱，导致自身免疫异常疾病，如类风湿性关节炎（RA），重症肌无力，红斑狼疮，痛风，多皮硬化症，视网膜炎等。目前治疗这类疾病主要为抑制异常并且亢进的免疫系统，治疗RA的药物有消炎镇痛和激素类的非特异性药物; 制剂和中药制剂的特异性药物。又分为一线药物和二线药物，临床上分为甾体类，非甾体类抗炎药物，症状缓解药物以及免疫抑制剂或调节剂，采用口服某些外源蛋白质，通过肠粘膜上淋巴组织，激活T细胞，释放出抑制性细胞素，降低患者病灶处的发炎细胞数，从而抑制炎症反应。目前，采用口服外源蛋白质治疗此类疾病的研究有：牛髓磷脂蛋白治疗多皮硬化症，鸡Ⅱ型胶原蛋白治疗RA，牛S抗原治疗视网膜炎，碱性髓磷脂蛋白治疗脑脊髓炎，人胰岛素治疗I型糖尿病等。口服Ⅱ型胶原蛋白治疗RA已进入临床研究，显示了明显的药效作用并具有良好的安全性。由于口服某些抗原蛋白而产生免疫耐受反应，机理明确，疗效显著，不良反应小，这类药物极有可能临床用于治疗各种自身免疫异常疾病的常用药物。     

09092 欧洲的自身免疫疾病治疗药市场将增长

根据Frost＆Sallivan一篇新的报告，欧洲的自身免疫疾病治疗药市场将因患者基数的扩大、认识的逐步提高和生物药逐渐被医师接受等各种因素刺激而增长。它指出，自身免疫疾病有70多种，包括类风湿性关节炎及多发性硬化病，根据目前的知识足以产出创新、有效和经济的治疗药物。     

自身免疫病患者可抽提核抗体谱与体液免疫的关系探讨

目的研究自身免疫病患者可抽提核抗体谱与体液免疫的关系。方法 70例自身免疫病患者,采用欧蒙免疫印迹法对其与30例正常人血清进行抗核抗体谱检测,对比观察两组患者的自身免疫性疾病分布情况。结果在抗核抗体谱检查结果中,多项抗可溶性抗原多肽抗体存在阳性表现,其中阳性率最高的为SSA抗体,占81.58%,其次为μl-r RNP抗体、Histone抗体、Nukleosomen抗体,分别占50.00%、42.11%、39.47%。结论就自身免疫病患者来讲,对其进行抗核抗体谱检测有一定的提示性诊断作用,且抗核抗原抗体阳性患者存在体液免疫应答增加。     

自身免疫性甲状腺病的研究进展

自身免疫性甲状腺病（AITD）是一组常见的器官特异性自身免疫性疾病,但其发病机制尚未完全明了,其临床表现复杂容易误诊。目前认为细胞因子、细胞凋亡、微量元素和遗传或易感因素等可能参与了AITD发生过程。本文就此展开综述。     

程序性死亡分子1及其配体与自身免疫病的研究进展

程序性死亡分子1 (programmed death-1,PD-1)及其配体(programmed death-1 ligand,PD-L)是一对新近研究较多的负性共刺激分子.PD-1与其配体结合后,传导的信号能抑制T淋巴细胞增殖,在调节T细胞活化和免疫耐受过程中发挥关键作用,从而对防止自身免疫病的发生、发展具有重要作用.PD-1/PD-L在免疫调节中的作用使其有望成为治疗免疫性疾病新的靶向分子.     

大剂量环磷酰胺冲击治疗三种自身免疫病的临床研究报告

目的　观察大剂量环磷酰胺冲击治疗自身免疫病的长期疗效。方法　选择难治性或复发性原发性血小板减少性紫癜 4 0例 ,难治性或复发性自身免疫性溶血性贫血 10例 ,狼疮性肾炎或重症系统性红斑狼疮 2 0例 ,用CTX 0 5～ 1 5 g/m2 体表面积 ,快速静滴 ,2h滴完 ,同时嘱大量饮水 ,每 4周 1次 ,最多为 4次。治疗前后自身对照。结果　ITP、AIHA、SLE长期疗效上差异均有非常显著意义 (P <0 0 1)。总有效率87%。结论　研究结果表明 ,大剂量CTX冲击治疗自身免疫症长期疗效显著、安全、操作简便、经济适用。     

T-bet对免疫细胞分化的调节及其与自身免疫病的关系

T盒转录因子T-bet是Th1型免疫的关键调节因子,在T淋巴细胞、B淋巴细胞、树突状细胞、NK细胞效应细胞的建立和维持中发挥着极其重要的作用,一些自身免疫病,特别是典型的与Th1免疫相关的疾病,其发病需要T-bet参与,这些在动物模型中得到证实。在此,就T-het在免疫细胞分化和自身免疫病发病机制中的作用及其在干预治疗中的可行性做一综述。     

Investigational C-C chemokine receptor 2 antagonists for the treatment of autoimmune diseases

Background: C-C chemokine receptor 2 (CCR2) antagonists belong to a group of chemokine blockers, which represent a new strategy for inflammatory diseases treatment by interfering with the complex system of chemokines and their receptors. A number of CCR2 antagonists are being developed for treatment of autoimmune diseases by different pharmaceutical and biotechnological companies. Objective: In this article the dark and the bright side of therapeutic CCR2 antagonism is discussed, with a view to its potential efficacy in various autoimmune diseases, in which clinical trials are already in progress, such as multiple sclerosis and rheumatoid arthritis. We describe different modes of possible interactions with CCR2–chemokine CC motif ligand 2 (CCL2) axis, usefulness of experimental animal models, continuing clinical trials and future perspectives of CCR2 antagonists. Methods: Until now only a few peer-reviewed articles providing data on the progress of preclinical and clinical trials with CCR2 antagonists have been published; therefore, we also present data based on preliminary reports, obtained from a number of press releases, conference communications and from the PharmaProjects database. Results/Conclusion: Although there is growing evidence for a great therapeutic potential of CCR2 blockade in autoimmune diseases, especially well documented in experimental animal models, so far clinical trials with CCR2 antagonists in humans have been moderately encouraging or even disappointing, indicating a need to further elucidate the complex system of chemokine interactions.     

网络药理学在中医药治疗自身免疫性疾病中的应用

自身免疫病发病机制复杂,缺乏特异标志物和新的治疗靶点。传统中医药治疗自身免疫病等慢性复杂疾病疗效良好,但其作用机制未明。网络药理学的核心思想与中医整体哲学有很多相通之处,作为新兴学科为中医药从经验医学向循证医学体系转化提供了新的研究模式。网络药理学应用于众多领域的研究,在某一类疾病中的应用却鲜有综述,通过检索国内外文献,本文综述了网络药理学在类风湿关节炎、银屑病、系统性红斑狼疮中医药防治以及相关生物学靶标筛选中的应用。     

Targeting IL-6 in the treatment of inflammatory and autoimmune diseases

Background: IL-6, a glycoprotein composed of 212 amino acids in human, has a wide range of biological activity, including regulation of immune response, support of hematopoiesis, generation of acute-phase reactions and induction of inflammation and oncogenesis. Several approaches including inhibition of IL-6 production, blockage of IL-6 binding to IL-6 receptor, blockage of IL-6/IL-6R complex binding to gp 130 and blockage of the intracytoplasmic signal through gp 130 can be used to block IL-6 functions. Objective: To summarize pre-clinical development and efficacy and safety of anti-IL-6 therapies in the treatment of inflammatory and autoimmune diseases. Methods: Journal articles found within a PubMed search and data presented in abstract form from international conferences up to May 2009 are described in this review. Results/conclusions: Tocilizumab, which blocks IL-6 binding to IL-6 receptor, used as monotherapy or in combination with methotrexate for RA therapy leads to significant clinical response and amelioration of joint damage, which is superior to methotrexate. Some adverse events such as liver function disorders, hyperlipidemia, neutropenia, diarrhea and infection are observed in clinical trials. IL-6 blockers targeting directly IL-6 rather than the IL-6 receptor and fully human monoclonal antibody targeting the IL-6 receptor are currently under development. Overall, targeting IL-6 has provided a promising approach in the management of some inflammatory and autoimmune diseases.     

白芍总苷的药理作用及其在自身免疫性疾病中的应用

研究发现白芍总苷具有多途径抑制自身免疫反应 ,以及抗炎、止痛、保肝的作用 ,对类风湿性关节炎 (RA)、系统性红斑狼疮 (SLE)等自身免疫病有确切疗效。本文对白芍总苷在细胞、体液免疫 ,抗炎等方面的基础研究 ,以及在自身免疫病治疗的临床研究予以综述     

糖皮质激素治疗系统性红斑狼疮致血脂异常的研究进展

血脂异常是系统性红斑狼疮患者应用糖皮质激素治疗引起的较为常见的并发症。长期大量的使用外源性糖皮质激素引起了胰岛素抵抗并且抑制了血中胆固醇的转化,从而影响了总胆固醇(TC)、总甘油三酯(TG)、低密度脂蛋白(LDL)和高密度脂蛋白(HDL)水平,造成血脂异常。随着糖皮质激素在临床上的广泛应用,系统性红斑狼疮患者的血脂异常发生率也在不断升高,该文就其研究现状及发病机制等予以综述。     

Pharmacological insights into autophagy modulation in autoimmune diseases

As a cellular bulk degradation and survival mechanism, autophagy is implicated in diverse biological processes. Genome-wide association studies have revealed the link between autophagy gene polymorphisms and susceptibility of autoimmune diseases including systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), indicating that autophagy dysregulation may be involved in the development of autoimmune diseases. A series of autophagy modulators have displayed protective effects on autoimmune disease models, highlighting the emerging role of autophagy modulators in treating autoimmune diseases. This review explores the roles of autophagy in the autoimmune diseases, with emphasis on four major autoimmune diseases [SLE, rheumatoid arthritis (RA), IBD, and experimental autoimmune encephalomyelitis (EAE)]. More importantly, the therapeutic potentials of small molecular autophagy modulators (including autophagy inducers and inhibitors) on autoimmune diseases are comprehensively analyzed.     

Leflunomide and teriflunomide: altering the metabolism of pyrimidines for the treatment of autoimmune diseases

Leflunomide modulates T-cell responses and induces a shift from the Th1 to Th2 subpopulation. This process results in a beneficial effect in diseases in which there is good evidence that T cells play a major role in both initiation and perpetuation of the inflammatory condition. Leflunomide has been successfully used for treating rheumatoid arthritis and psoriatic arthritis for many years. The active metabolite of leflunomide is teriflunomide, which has been approved for treating multiple sclerosis. Teriflunomide, just like the mother drug, inhibits dihydro-orotate dehydrogenase and synthesis of pyrimidine. The present review presents and discusses the safety profiles of leflunomide and teriflunomide, two drugs that are indeed the same, considering that much can be learned from the reported side effects of both.     

B细胞耐受原阿贝莫司钠的研究现状及启示

阿贝莫司钠(abetimus sodium,LJP-394)是美国La Jolla制药公司历时20多年研究开发的拟用于治疗系统性红斑狼疮的新药。阿贝莫司钠属于B细胞耐受原,可与B细胞抗dsDNA抗体交联而诱导B细胞产生免疫耐受。在Ⅲ期临床试验中,阿贝莫司钠能降低部分狼疮性肾炎患者抗dsDNA抗体水平,但对肾炎复发无明显的保护作用。因此,2009年La Jolla制药公司宣布终止了阿贝莫司钠的临床试验。本文对就阿贝莫司钠的作用特点和研究脉络作一综述,为研究开发治疗系统性红斑狼疮的新药提供借鉴。     

那他珠单抗治疗多发性硬化研究进展

α4β1整合素在多发性硬化发病机制的最早环节中起关键作用,阻断α4整合素可防止自身免疫细胞通过与中枢神经的微血管粘附而进入中枢神经系统,从而减轻炎症性脱髓鞘反应。那他珠单抗是针对整合素的α4亚单位的单克隆抗体,临床试验表明主要通过抑制粘附过程而防止出现新病灶,对已有病灶也有减轻炎症反应的作用,从而减少复发。