Larché Mark
Department of Allergy and Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, United Kingdom.
Pharmacol Ther. 2005 Dec;108(3):353-61. doi: 10.1016/j.pharmthera.2005.05.004. Epub 2005 Jul 12.
Desensitising allergen immunotherapy has been practised for many decades. Although time consuming, this form of therapy is antigen-specific and disease-modifying, in contrast to palliative pharmacotherapy. However, the use of allergen extracts containing native allergen molecules frequently results in allergic adverse reactions to treatment. Several strategies to reduce the allergenicity of therapeutic preparations, while maintaining their therapeutic benefit, are being developed. Peptide immunotherapy is one such approach. Short synthetic peptides, comprising T cell epitopes of major allergens, were unable to crosslink allergen-specific IgE molecules on basophils in vitro. Treatment of allergic volunteers with allergen peptides resulted in reduced skin, lung and nasal sensitivity to allergen challenge and improved their subjective ability to tolerate allergen exposure. Peptides reduced pro-inflammatory cytokine secretion from peripheral blood cells, whilst increasing the immunosuppressive cytokine IL-10. Furthermore, peptide therapy was associated with the induction of a population of CD4+ T cells with a suppressive functional phenotype. Thus, peptide therapy may be suitable for the antigen-specific treatment of allergic diseases.
脱敏变应原免疫疗法已经应用了数十年。尽管这种疗法耗时,但与姑息性药物治疗不同,它是抗原特异性的且能改变疾病进程。然而,使用含有天然变应原分子的变应原提取物常常会导致治疗过程中的过敏不良反应。目前正在研发多种策略,以在保持治疗效果的同时降低治疗制剂的变应原性。肽免疫疗法就是其中一种方法。由主要变应原的T细胞表位组成的短合成肽,在体外无法使嗜碱性粒细胞上的变应原特异性IgE分子交联。用变应原肽治疗过敏志愿者,可降低皮肤、肺部和鼻腔对变应原激发的敏感性,并提高他们耐受变应原暴露的主观能力。肽可减少外周血细胞促炎细胞因子的分泌,同时增加免疫抑制细胞因子IL-10的分泌。此外,肽疗法与诱导具有抑制性功能表型的CD4+T细胞群体有关。因此,肽疗法可能适用于变应性疾病的抗原特异性治疗。