特异性免疫治疗机制的研究进展

特异性免疫治疗是治疗过敏性疾病的最有效方法,至今已有90多年的历史.其机制尚未明确,早期的研究重点集中于循环抗体和效应细胞,目前主要集中于免疫治疗对T细胞的作用及由此引起的一系列细胞因子的变化、CD4+调节性T细胞亚群、修饰抗原递呈细胞诱导免疫耐受、免疫效应细胞募集机制、单克隆技术支持下的重组变应原、变应原DNA疫苗、...     

儿童支气管哮喘的免疫疗法及其进展

支气管哮喘(哮喘)的免疫疗法分特异性和非特异性两类,特异性免疫疗法目前的进展主要集中于研究作用机制以及纯化优化变应原制剂这两个方面.随着哮喘分子及细胞免疫学机制研究的日益深入,各种新的非特异性免疫治疗策略也层出不穷,其中抗IgE单克隆抗体发展最为成熟,已获得美国食品药品管理局认可用于中、重度哮喘的治疗.其他如抗免疫刺激序列DNA疫苗、辅助T细胞2型细胞因子疗法和抗T细胞疗法等也陆续投入哮喘治疗的研究.该文对特异性免疫疗法和非特异性免疫疗法及其研究进展进行综合性评述,并总结免疫疗法的进一步发展方向.     

支气管哮喘特异性免疫治疗的研究进展

目前,通过调节辅助T细胞Th1/Th2平衡和介导免疫耐受等机制治疗支气管哮喘的特异性免疫治疗(STT)越来越引起人们的重视,SIT通过皮下注射和舌下含服变应原疫苗等给药方式区别于糖皮质激素的吸入治疗.STT虽然还存在局部或全身等不良反应和仅作为吸入激素的辅助和附加治疗,但因其具有疗效肯定、持久等特点,随着STT制剂的标准化、治疗的规范,SIT将具有广阔的应用前景.     

变应原特异性免疫治疗在儿童变应性疾病中的应用

变应原特异性免疫治疗是一种应用于IgE介导的变应性疾病的脱敏疗法,其主要和药物治疗联合使用,治疗过敏原无法避免的变应性哮喘、变应性鼻炎及特发性皮炎患者,也是可能改变变应性疾病自然病程的治疗方法.但是免疫治疗在儿童过敏性疾病中的应用尚存在争议,研究较少.现就变应原特异性免疫治疗的作用机制及其在儿童变应性疾病中的临床疗效和安全性进行综述.     

特异性免疫治疗在过敏性疾病中的作用研究进展

特异性免疫治疗是目前惟一一种针对过敏性疾病的对因、对症治疗方法,包括特异性皮下免疫治疗及特异性舌下免疫治疗.研究证实特异性舌下免疫治疗在过敏性疾病中疗效肯定,其通过产生特异性抗体,调节变应原特异性T细胞的反应类型而发挥抗过敏作用,而且不良反应相对较轻,近年来应用较为普遍.

Abstract：

The specific immunotherapy is the etiological treatment and remission the symptoms of anaphylactic disease. It includes subcutaneous immunotherapy and sublingual immunotherapy(SLIT). SLIT is a new pathway. Many studies have confirmed its effectiveness in the treatment of anaphylactic disease. Due to its mild side effect, it is used commonly.     

变应原特异性免疫治疗

变应原特异性免疫治疗是唯一可以改变变态反应性疾病进程的治疗方法,随着近年来变应原制剂质量及标准化程度的提高,使其不良反应更小、更适合临床应用.由于儿童患者正处于生长发育期,其免疫系统发育尚未完全,是接受变应原特异性免疫治疗的最佳时期,治疗效果较成人好.皮下注射的变应原特异性免疫治疗经多年的实践和研究,疗效公认;而目前已逐渐成熟的舌下脱敏治疗和皮下注射脱敏治疗的疗效一样,并得到儿童的喜爱.寻找到引起患者临床症状的主要变应原,用该抗原进行脱敏治疗方可达到预期的治疗目的.     

标准化变应原皮肤试验与哮喘儿童年龄的关系

目的 探讨标准化变应原皮肤试验结果与哮喘儿童年龄的关系,为避免接触变应原及进行早期特异性免疫治疗提供参考依据.方法 对重庆医科大学附属儿童医院哮喘门诊2005年6月-2007年1月收治的913例哮喘患儿采用欧州丹麦ALK-ABELLO公司提供的13种标准化变应原皮肤点刺液进行试验,以变应原及组胺所致风团直径比判定其反应级别.分析各变应原的阳性率、皮肤指数(SI)、变应性哮喘的危险因素及各年龄组变应原SI和阳性项数.采用SAS 8.2软件进行统计学分析.结果 粉尘螨、屋尘螨和热带螨阳性率和SI分别居前3位.年龄是变应性哮喘的危险因素,其OR值为1.16,95%Cl为1.09～1.24.>5岁哮喘儿童变应原SI显著高于≤5岁哮喘儿童(Z=5.68 P<0.01).2～8岁组哮喘患儿,无论变应原SI还是阳性项数都逐渐增加,其中>5～8岁组哮喘患儿变应原SI和阳性项数水平高且增长快,>8～10岁为高峰平台期,10岁后则呈下降趋势.结论 年龄是变应性哮喘的危险因素.>5岁哮喘患儿的变应原SI显著高于≤5岁哮喘患儿.>5～8岁为变应性哮喘患儿特异性免疫治疗的最佳年龄期.应抓住这个特异性免疫治疗的窗口年龄期,尽早进行特异性免疫治疗.     

儿童食物过敏免疫治疗研究进展

儿童食物过敏的发生率逐年增加,目前对食物过敏的治疗主要是缓解症状而难以治愈.随着分子免疫学的发展及对食物过敏发生机制等的深入研究,一些行之有效的治疗措施正应用于临床.该文就食物过敏的免疫治疗方法,包括T细胞肽及重组致敏蛋白突变免疫疗法、免疫刺激的DNA序列、辅助T细胞激活作用的抑制、过敏诱导的细胞因子的抑制及炎性细胞迁移的抑制等作一综述.     

变应原免疫治疗的作用机制及临床应用进展

变应原免疫治疗(allergen immunotherapy,AIT)是一种治疗过敏性疾病的有效治疗方法,其应用已有1个多世纪。目前AIT主要有两种给药方式:皮下注射免疫治疗(subcutaneous immunotherapy,SCIT)和舌下含服免疫治疗(sublingual immunotherapy,SLIT),其目的是诱导患者对变应原的免疫耐受,给患者带来长期的临床益处。AIT的有效性已有大量的循证医学证据证实,对其作用机制的研究也不断深入,AIT联合生物制剂等在临床已有较为广泛的应用。     

免疫药物治疗胰岛残存胰岛β细胞研究进展

1型糖尿病患者胰岛β细胞功能和数量均降低,即使早期使用胰岛素,也不能避免严重并发症发生.免疫治疗不同于以往的替代疗法,侧重于重建机体病态T细胞和免疫调节效应的平衡,抑制针对胰岛β细胞的自身免疫反应,增强胰岛β细胞对自身免疫的耐受.目前,多种免疫药物已经被批准用于治疗1型糖尿病,如抗CD3单克隆抗体、GAD-alum等.     

Oral immunotherapy in hen’s egg‐allergic children increases a hypo‐proliferative subset of CD4+ T cells that could constitute a marker of tolerance achievement

Background: Food allergy affects a significant number of children and its prevalence, and persistence is undergoing an important increase in the last years. Specific oral tolerance induction (SOTI) is a promising therapy for food allergy. However, little is known about the immune mechanisms implicated in the desensitization to allergens. Our purpose was to study which immune parameters are modified during the process of tolerance achievement with the goal of identifying markers of tolerance induction. Methods: We performed an extensive immune analysis in 19 allergic children following SOTI with hen’s egg before and after the immunotherapy. Changes in lymphocyte subpopulations and serum cytokines were identified in children with desensitization achievement. Results: Sixteen children achieved complete tolerance to egg, and the immune analysis reveals that desensitization was accompanied in all the cases by a significant decrease in the percentage and absolute counts of effector‐memory CD4+ T cells (T_EM) and a marked increase in the absolute counts of a subset of CD4⁺CD38⁺CD45RO^? cells. Additionally, we also observed a marked reduction in the plasma levels of different Th1 and Th2 cytokines after tolerance achievement. Conclusions: Acquisition of tolerance in children after oral immunotherapy is accompanied by a decrease in the T_EM population and the increase in a particular subset of CD4+ T cells with a hypo‐proliferative and non‐reactive phenotype. This hypo‐proliferative subset of cells could constitute a marker of the development of oral tolerance, and the study of this subset could contribute to the better understanding of the immune responses in allergic subjects.     

Hyposensitization: indications and expectations

Allergy is the most frequent immunologic disorder in childhood. The prevalence of allergic complaints among children is estimated as about 10%. The diagnosis of an allergy takes the following factors into account: The patient's history, skin test, determination of total and specific IgE antibodies and a provocation test to a diseased organ. Hyposensitization is recommended for allergic patients without any significant improvement in spite of avoidance of allergen and in spite of pharmacologic therapy. Modified allergens/allergoids demonstrate a comparable efficacy as a conventional subcutaneous allergen immunotherapy. Measurement of specific IgE- and IgG-antibodies permits an evaluation of degree of sensitization and/or immune response to hyposensitization treatment.     

Possible alternatives to antimicrobial therapies

The care of immunosuppressed patients has constantly improved over the years, and pharmacologic developments contributed significantly to this success. However, despite these advances, current anti-infectious agents are limited in their efficacy by either weak specificity or side effects, including suppression of bone marrow function. Control of infection will ultimately depend on reconstitution of specific immunity. Thus, adoptive cellular immunotherapy represents an attractive, low-toxicity strategy to restore specific immune surveillance, and prevent/treat potentially life-threatening disease due to pathogens relevant to the immunosuppressed host.Evidence derived from trials conducted in recipients of hematopoietic stem cell transplantation indicate that adoptive transfer of antigen-specific T cells is a feasible and safe strategy to restore protective immunity and prevent or reverse virus-associated disease.Despite the great potential, immunotherapy for viral and fungal disease still has a marginal role in the management of immunosuppressed patients. This is due to limitations inherent to the technologies and products employed, and, more importantly, to the financial and structural requirements that are associated with GMP production. However, cell therapy offers a unique opportunity to restore antipathogen immune surveillance, and it is therefore conceivable that application of this strategy will increase in the next few years.     

Dendritic cells modifi cation during sublingual immunotherapy in children with allergic symptoms to house dust mites

Background

The importance of dendritic cells (DCs) in the initiation of the Th2-mediated inflammatory response to allergens is well known and more recently it has been proposed that DCs have a pivotal role in maintaining tolerance to allergens. The aim of this study was to investigate whether the success of sublingual immunotherapy (SLIT) in allergic asthma is mediated by the induction of changes of DCs functions.

Methods

Ten children with allergic asthma sensitive to house dust mite were studied before and after 12 months of SLIT. Immature DCs were derived from peripheral blood monocytes cultured for 6 days in presence of interleukin (IL)-4 and GM-CSF and stimulated with lipopolysaccharide for the last 24 hours to induce maturation.

Results

After 12 months of SLIT, mature DCs derived from SLIT-treated patients showed a statistically significant defect of CD86 up-regulation, an increase of IL-10, and a reduction of IL-12 production.

Conclusion

SLIT induces changes in DCs functions that might be responsible for an impairment of T cell activation or drive T cells towards a regulatory activity, thus restoring immune tolerance to allergens.     

特异性免疫治疗新进展

特异性免疫治疗(SIT)作为目前唯一可能根治变应性疾病的治疗方法,不仅可以减轻过敏症状,减少用药,还可阻止自然病程的进展,预防新变应原的产生.近年来舌下SIT因其良好的安全性、有效性和易操作性已在欧洲各国广泛开展.标准化的变应原制剂在国内外逐步应用,已取代非标准化制剂.然而无论是皮下注射还是舌下含服方法,其具体有效剂量、治疗方案、治疗疗程尚待规范统一.随着对其作用机制的不断深入研究,以及以重组变应原为主的新制剂的研发,SIT的应用范围将会进一步扩大,更好地用于变应性疾病的治疗.     

Immunotherapy with virus-specific cytotoxic T lymphocytes after organ transplantation

Adoptive immunotherapy with antigen specific cytotoxic T lymphocytes can favorably impact the outcome of serious herpesvirus infections in organ transplant recipients. Current challenges in this field include the determination of which patients are at highest risk, and the development of protocols that permit more rapid expansion of virus specific effector cells.     

Marche allergique chez l’enfant,de la rhinite à l’asthme : prise en charge,place de la désensibilisation

Allergic rhinitis (AR) is a common IgE dependent disorder. AR is maybe one of the steps of the allergic march, which starts with atopic dermatitis and food allergy and includes atopic asthma. AR and asthma are frequently associated. AR is frequently under-diagnosed and undertreated although it affects quality of life and school performance. Management of AR depends on its severity and will associate environmental control (best guided by environmental investigation and skin testing of specific IgE antibodies), pharmacotherapy (with antihistamines and intranasal corticosteroids as first line drugs). At present allergen immunotherapy is considered in patients with severe AR, insufficiently controlled by pharmacotherapy and who demonstrate specific IgE antibodies to relevant allergens. Sublingual immunotherapy is well tolerated. Only immunotherapy with the right allergens has the potential to alter the natural history of the allergic march, by preventing the development of new allergen sensitizations and reducing the risk for the subsequent development of asthma. This fact might extend the indications of specific allergen immunotherapy. Patients (and parents) education is of utmost importance in the management of allergic disorders.     

鼻病毒感染与儿童哮喘急性加重机制

人鼻病毒(HRV)感染是哮喘急性发作和(或)加重的重要诱发因素,但其致病机制极其复杂,除鼻病毒的直接作用及因炎性介质释放和炎性细胞浸润而导致机体的炎症反应外,HRV感染诱导机体的异常免疫反应特别是Th1/Th2免疫失衡及调节性T细胞功能异常已受到研究者们的广泛重视.深入研究HRV感染所诱导的儿童哮喘急性发作,对阐明哮喘的发病机制及探索疾病免疫治疗有重要意义.