Müller U, Akdis C A, Fricker M, Akdis M, Blesken T, Bettens F, Blaser K
Medical Division, Zieglerspital, Bern, Switzerland.
J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):747-54. doi: 10.1016/S0091-6749(98)70402-6.
Specific immunotherapy with honeybee venom (BV) is highly effective, but allergic side effects can occur during treatment. Immunotherapy with peptides containing major T-cell epitopes of the relevant allergen or allergens provides an alternative strategy without these problems.
The study investigates the immunologic mechanisms and clinical effects of immunotherapy with T-cell epitope peptides of the major BV allergen, the phospholipase A2 (PLA).
Five patients with IgE-mediated systemic allergic reactions to bee stings were treated with a mixture of three T-cell epitope peptides of PLA. Ten patients allergic to BV receiving whole BV immunotherapy served as control subjects. Increasing doses of the peptide mixture, up to a maintenance dose of 100 microg, were administered subcutaneously within 2 months. The patients were then challenged with PLA and 1 week later with a bee sting. The cellular and humoral immune response was measured in vitro.
No allergic side effects were caused by the peptide immunotherapy, and all patients tolerated the challenge with PLA without systemic allergic symptoms. Two patients developed mild systemic allergic reactions after the bee sting challenge. After peptide immunotherapy, specific proliferative responses to PLA and the peptides in peripheral blood mononuclear cells were decreased in successfully treated patients. The production of TH2 and TH1 cytokines was inhibited, and B cells were not affected in their capacity to produce specific IgE and IgG4 antibodies. Their levels increased after allergen challenge in favor of IgG4.
Immunotherapy of BV allergy with short T-cell peptides of PLA induces epitope-specific anergy in peripheral T cells and changes the specific isotype ratio in a fashion similar to that of conventional immunotherapy in successfully treated patients.
蜜蜂毒液（BV）特异性免疫疗法非常有效，但治疗期间可能会出现过敏副作用。使用含有相关变应原主要T细胞表位的肽进行免疫疗法提供了一种没有这些问题的替代策略。
本研究调查主要BV变应原磷脂酶A2（PLA）的T细胞表位肽免疫疗法的免疫机制和临床效果。
5例对蜂蜇有IgE介导的全身过敏反应的患者用PLA的三种T细胞表位肽混合物进行治疗。10例对BV过敏并接受全BV免疫疗法的患者作为对照。在2个月内皮下注射递增剂量的肽混合物，直至维持剂量100μg。然后让患者接受PLA激发，1周后接受蜂蜇激发。体外测量细胞和体液免疫反应。
肽免疫疗法未引起过敏副作用，所有患者对PLA激发均能耐受，无全身过敏症状。2例患者在蜂蜇激发后出现轻度全身过敏反应。肽免疫疗法后，成功治疗的患者外周血单个核细胞对PLA和肽的特异性增殖反应降低。TH2和TH1细胞因子的产生受到抑制，B细胞产生特异性IgE和IgG4抗体的能力未受影响。变应原激发后其水平升高，有利于IgG4。
用PLA的短T细胞肽对BV过敏进行免疫疗法可在外周T细胞中诱导表位特异性无反应性，并以与成功治疗患者的传统免疫疗法类似的方式改变特异性同种型比例。
