抗细胞因子自身抗体

输注重组细胞因子可导致患者产生抗细胞因子自身抗体,T细胞免疫耐受的消失是健康个体含有高亲和力抗细胞因子自身抗体的原因,从而导致输注IgG制品者体内含有多种抗细胞因子自身抗体,造成细胞因子治疗失效.细胞因子疫苗可用于抗细胞因子治疗.临床上值得关注的是,抗细胞因子抗体会干扰某些细胞因子的测定,某些抗细胞因子抗体水平可判断免疫炎性疾病的预后.     

抗细胞因子自身抗体

输注重组细胞因子可导致患者产生抗细胞因子自身抗体,T细胞免疫耐受的消失是健康个体含有高亲和力抗细胞因子自身抗体的原因。从而导致输注IgG制品者体内含有多种抗细胞因子自身抗体,造成细胞因子治疗失效。细胞因子疫苗可用于抗细胞因子治疗,临床上值得关注的是,抗细胞因子抗体会干扰某些细胞因子的测定。某些抗细胞因子抗体水平可判断免疫炎性疾病的预后。     

生物技术方法治疗自身免疫性疾病的研究进展

自身免疫性疾病是一种由于机体免疫应答失控而引起的一类疾病。传统的免疫抑制剂治疗由于存在副反应多等缺点,已不能满足人们的需求。随着生命科学的发展,应用生物技术治疗自身免疫性疾病已成为当前治疗该类疾病的主流趋势,如针对T淋巴细胞、B淋巴细胞、细胞因子的治疗方法,又如肿瘤坏死因子以及各类白细胞介素均可以作为治疗自身免疫性疾病的靶点。目前已经有3种肿瘤坏死因子的抗体作为治疗自身免疫性疾病的药物上市。并取得了令人肯定的疗效。另外,随着基因以及疫苗技术的发展,采用基因以及疫苗治疗的方法应用于自身免疫性疾病也取得了一定的成果。目前,应用生物技术质量自身免疫性疾病已成为当前质量该类疾病的主流趋势。文章就应用生物技术对自身免疫性疾病进行治疗作了简要综述。     

白细胞介素-2及其相关药物的应用研究进展

综述白细胞介素-2及抗白细胞介素-2受体单克隆抗体的应用研究进展。白细胞介素-2是一种在机体的免疫调节中发挥着重要而复杂作用的细胞因子,既可促进淋巴细胞增殖,增强免疫功能,又能限制T细胞反应而增强机体的免疫耐受,故可用于治疗肿瘤和感染性疾病及自身免疫性疾病。     

常用免疫抑制剂在皮肤科中的应用

免疫抑制剂（immunosuppressive agent）是一种能抑制机体免疫功能的生物或非生物制剂,主要用于器官移植后抗排斥反应或自身免疫性疾病的治疗。随着医药行业发展,免疫抑制剂的家族不断扩大,治疗效果也取得很大进展。迄今为止,免疫抑制剂的研究已有近一个世纪的历史,它不断从低选择性向高选择性发展,从高毒性向低毒性发展。免疫抑制剂在皮肤科主要用于各种结缔组织病和变态反应性疾病及皮肤肿瘤等的治疗。     

系统性红斑狼疮患者血清可溶性细胞间黏附分子-1、L-选择素及细胞因子浓度测定的临床意义

系统性红斑狼疮（systemic lupus erthmatosus。SLE）是一种以B淋巴细胞度活化，以抗dsDNA、抗sm等自身抗体为特征的、机体免疫调节系统紊乱所致的多系统受累的自身免疫性疾病。其中黏附分子则参与了T、B细胞活化以及T、B细胞之间的相互作用。细胞因子是各细胞产生的可溶性物质，体内各种反应均需要其参与。近来黏附分子和细胞因子在SLE中作用的研究日益受到重视。     

抗IL—2和抗TNF—α自身抗体检测及临床初步观察

细胞因子(cytokines,CK)是一免疫功能调节物,由淋巴细胞、单核细胞及其他细胞产生,其中包括白细胞介素、干扰素、肿瘤坏死因子、集落刺激因子及多种生长因子。80年代初,发现正常人和某些自身免疫性疾病、感染性疾病、肿瘤及经CK治疗后的患者体内存在抗CK抗体,包括抗IL-1、抗IL-2、抗IL-6、抗TNF-α等。有关细胞因子自身抗体     

英夫利西单抗治疗类风湿关节炎、强直性脊柱炎与克罗恩病

肿瘤坏死因子α(TNF-α)是一种促炎细胞因子,在多种自身免疫性疾病中起重要的病理作用。英夫利西单抗(infliximab)是一种针对TNF-α、人鼠嵌合的单克隆抗体,和人体中多种形式的TNF-α具有很强的结合能力,可以很好的阻断TNF-α的病理作用,从而治疗疾病。在多项临床研究中,包括类风湿关节炎(RA)、强直性脊柱炎(AS)和克罗恩病(CD)的治疗试验中,英夫利西单抗都具有良好的疗效、可以减缓甚至阻断疾病的慢性破坏。此外,英夫利西单抗也逐渐试用于其他自身免疫性疾病并取得良好疗效,同时具有很高的耐受性和安全性。因此,英夫利西单抗是RA、AS和CD等自身免疫性疾病的治疗新选择。     

重组卡介苗

卡介苗（BCG）已成为可同时表达多种病原体重组抗原的新疫苗载体。本文概述了重组BCG研究进展，分别介绍了抗病毒、 细菌、寄生虫病重组BCG的构建和在动物中的免疫应答，分泌细胞因子的重组BCG用于抗肿瘤免疫治疗，重组的BCG也可发展为抗分枝杆菌感染的新疫苗,并提出了今后研究方向。     

罗米司亭的药理与临床评价

特发性血小板减少性紫癜(ITP)是一种自身免疫性疾病,系抗血小板抗体引起血小板破坏而导致严重的出血。常规的治疗是使用糖皮质激素、免疫抑制剂、抗人CD20单克隆抗体或脾切除,但这些疗法会引起复发或许多不良反应。最近的研究显示:血小板生成素是能调节血小板产生的细胞因子,罗米司亭是一种重组Fc肽融合蛋白,能增加慢性ITP患者的血小板数量。文中综述了其作用机制、药效学、药动学和临床评价。     

Therapeutic vaccines: realities of today and hopes for the future

Vaccines are by definition prophylactic, but in recent years an interest has developed in therapeutic vaccines for infectious diseases such as AIDS and tuberculosis, as well as gastric ulcers, cancer (with different approaches to combat various types of malignancy) and autoimmune diseases (a definite success was the development of a vaccine against multiple sclerosis) and there are potential vaccines in development for myasthenia gravis, lupus and diabetes. Therapeutic vaccines are also being developed against cognitive diseases such as Alzheimer's disease, prion diseases and Huntington's disease. All of these efforts are based on the therapeutic vaccine being closely related chemically to the etiological agent that causes the disease.     

肠道细菌性疫苗研究进展

人肠道致病菌具有高度传染性，可引起多种疾病。目前已有多种肠道细菌灭活疫苗和减毒活疫苗通过安全性评价上市；重组蛋白疫苗、结合疫苗和亚单位疫苗等新型疫苗的研究已获得较好的结果。此文对人肠道致病菌及其相关新疫苗的研究进展做一综述。     

Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases

Apart from cancer chronic (auto)immune-mediated diseases are a major threat for patients and a challenge for physicians. These conditions include classic autoimmune diseases like systemic lupus erythematosus, systemic sclerosis and dermatomyositis and also immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis. Traditional therapies for these conditions include unspecific immunosuppressants including steroids and cyclophosphamide, more specific compounds such as ciclosporin or other drugs which are thought to act as immunomodulators (fumarates and intravenous immunoglobulins). With increasing knowledge about the underlying pathomechanisms of the diseases, targeted biologic therapies mainly consisting of anti-cytokine or anti-cytokine receptor agents have been developed. The latter have led to a substantial improvement of the induction of long term remission but drug costs are high and are not affordable in all countries. In China an extract of the herb Tripterygium wilfordii Hook F. (TwHF) is frequently used to treat autoimmune and/or inflammatory diseases due to its favourable cost-benefit ratio. Triptolide has turned out to be the active substance of TwHF extracts and has been shown to exert potent anti-inflammatory and immunosuppressive effects in vitro and in vivo. There is increasing evidence for an immunomodulatory and partly immunosuppressive mechanism of action of triptolide. Thus, compounds such as triptolide or triptolide derivatives may have the potential to be developed as a new class of drugs for these diseases. In this review we summarize the published knowledge regarding clinical use, pharmacokinetics and the possible mode of action of triptolide in the treatment of inflammatory diseases with a particular focus on psoriasis.     

基于细胞毒性T淋巴细胞抗原4研发的生物制剂的临床应用进展

免疫疗法是一种快速发展的治疗自身免疫病和癌症的方法。细胞毒性T淋巴细胞抗原4（cytotoxic T lymphocyte antigen 4,CTLA-4）是适应性免疫应答的主要抑制分子,也是该领域最著名和研究最广泛的分子。CTLA-4能够通过多种机制来调节和控制免疫细胞的功能。随着对CTLA-4研究的深入,科学家已经研发出CTLA-4类似物阿巴西普和针对CTLA-4的抗体伊匹木单抗。这两种针对CTLA-4的生物制剂,在自身免疫病和肿瘤疾病的治疗中具有广阔的应用前景。     

Nucleic acid vaccination strategies against infectious diseases

Introduction: Gene vaccines are an interesting and emerging alternative for the prevention of infectious diseases, as well as in the treatment of other pathologies including cancer, allergies, autoimmune diseases, or even drug dependencies. When applied to the target organism, these vaccines induce the expression of encoded antigens and elicit the corresponding immune response, with the potential ability of being able to induce antibody-, helper T cell-, and cytotoxic T cell-mediated immune responses.

Areas covered: Special attention is paid to the variety of adjuvants that may be co-administered to enhance and/or to modulate immune responses, and to the methods of delivery. Finally, this article reviews the efficacy data of gene vaccines against infectious diseases released from current clinical trials.

Expert opinion: Taken together, this approach will have a major impact on future strategies for the prevention of infectious diseases. Better-designed nucleic acid constructs, novel delivery technologies, as well as the clarification of the mechanisms for antigen presentation will improve the potential applications of this vaccination strategy against microbial pathogens.     

肠道病毒及其疫苗研究进展

人肠道病毒具有高度传染性,可引起多种疾病。目前多种肠道病毒灭活疫苗、减毒活疫苗已通过安全性评价上市;亚单位疫苗、DNA疫苗、病毒样颗粒疫苗的研究已获得较好的结果。此文旨在对人肠道病毒及其流行病学特征,以及相关疫苗的研究进展做一综述。     

Live attenuated and inactivated viral vaccine formulation and nasal delivery: Potential and challenges

Vaccines are cost-effective for the prevention of infectious diseases and have significantly reduced mortality and morbidity. Novel approaches are needed to develop safe and effective vaccines against disease. Major challenges in vaccine development include stability in a suitable dosage form and effective modes of delivery. Many live attenuated vaccines are capable of eliciting both humoral and cell mediated immune responses if physicochemically stable in an appropriate delivery vehicle. Knowing primary stresses that impart instability provides a general rationale for formulation development and mode of delivery. Since most pathogens enter the body through the mucosal route, live-attenuated vaccines have the advantage of mimicking natural immunization via non-invasive delivery. This presentation will examine aspects of formulation design, types of robust dosage forms to consider, effective routes of delivery (invasive and noninvasive), and distinctions between live attenuated or inactivated vaccines.     

Aptamers against interleukin-12-related cytokines as novel therapeutics in autoimmune diseases

Endogenous interleukin (IL)-12 plays a pivotal role in promoting cell-mediated immunity against intracellular pathogens. Uncontrolled cell-mediated immune responses, however, may lead to chronic inflammation and autoimmune disease. Unfortunately, treatment of either infection or autoimmunity with immunomodulating drugs always incur the danger of favouring the other form of disease. The recent discovery of the dimeric IL-12-related cytokine IL-23 adds to our understanding of the fine tuning of cellular immunity. Only recently, studies revealed IL-23, and not IL-12, to be the decisive factor in this immune deviation and a variety of autoimmune disorders have now been shown to be strikingly dependent on IL-23. Therefore, targeting of IL-23-mediated, rather than IL-12-dependent, mechanisms represent a promising therapeutic approach for autoimmune diseases. The invention of aptamers that are capable of neutralising IL-23 and/or IL-12 and their potential use as autoimmune disease therapeutics will be discussed.     

The role of infections in the pathogenesis of autoimmune diseases

The autoimmune diseases result from inappropriate responses of the immune system to self antigens. The etiology of autoimmune diseases remains largely unknown but candidate etiologic factors include genetic abnormalities and infections. Although there are considerable data supporting the role of infections in a variety of autoimmune diseases, this role has been unequivocally established in only a few autoimmune diseases. The difficulty in establishing the infectious etiology of autoimmune diseases stems from several factors such as the heterogeneity of clinical manifestations in individual autoimmune diseases and the time interval between infection and autoimmune disease. The data on this association derive from clinical observations, epidemiological studies and research using laboratory techniques, protein sequence database screening and animal models. Infectious agents can cause autoimmune diseases by different mechanisms, which fall into two categories: antigen specific in which pathogen products or elements have a central role e.g. superantigens or epitope (molecular) mimicry, and antigen non-specific in which the pathogen provides the appropriate inflammatory setting for "bystander activation". The most important mechanisms are molecular mimicry and superantigens. As far as molecular mimicry is concerned the recent data on the degeneracy of T cell recognition shifted the focus from searching for linear sequence homology to looking for similarity of antigenic surfaces. Special mention has to be made to retroviruses as they have some unique means of inducing autoimmunity.     

Strategies for effective naked-DNA vaccination against infectious diseases

To date, vaccination is an active area of investigation for its application to a great variety of human diseases including infections and cancer. In particular, naked-DNA vaccination has arisen as effective strategy in the preventive medicine field with promising future prospects. The ability of plasmid DNA to activate the humoural and the cellular arms of the immune system against the encoded antigen have resulted in intensive study of new strategies aimed at increasing the DNA vaccine immunogenicity. Nevertheless, plasmid-based vaccines emerged as a safer and advantageous alternative with respect to viral vector vaccines. Recent advances in both the immunological and biotechnological research field made it possible to enhance significantly the DNA vaccine potency. Most of these approaches are based on both the discovery of novel delivery systems and the implementation of plasmid constructs, achieved through genetic engineering. In this review, we will describe some of the most relevant patents issued in the last ten years, supporting the progress made in naked-DNA vaccination against infectious diseases.