Hirai T, Yoshioka Y, Takahashi H, Handa T, Izumi N, Mori T, Uemura E, Nishijima N, Sagami K, Yamaguchi M, Eto S, Nagano K, Kamada H, Tsunoda S, Ishii K J, Higashisaka K, Tsutsumi Y
Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Vaccine Creation Project, BIKEN Innovative Vaccine Research Alliance Laboratories, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Clin Exp Allergy. 2016 Jul;46(7):992-1003. doi: 10.1111/cea.12722. Epub 2016 May 3.
The relationship among natural allergen exposure, induction of blocking antibody and the occurrence of atopic allergy-particularly in the presence of IgE production-is debatable.
To clarify the relationship between the dose of cutaneous exposure to dust mite allergen and susceptibility to the IgE-mediated allergic response in relation to IgG production.
NC/Nga mice were epicutaneously exposed to various doses of Dermatophagoides pteronyssinus allergen to induce atopic dermatitis-like skin lesions. We then evaluated the skin lesions, induction of mite-specific immune responses, and susceptibility to anaphylaxis.
Dose-dependent exacerbation of atopic dermatitis-like skin lesions and increases in mite-specific IgG and IgE production were observed. However, mice exposed to relatively low doses of mite allergen showed hypersusceptibility to mite allergen-specific anaphylaxis. We also showed that adoptive transfer of total IgG from Dp-sensitized mice rescued mice from the hypersusceptibility seen in those exposed to low doses of mite allergen.
High-dose cutaneous exposure to dust mites induced effective blocking IgG production, even if accompanied by IgE production. Our data might support the concept that an increase in IgG titre, not a decrease in IgE titre, is a marker of clinical improvement in allergen-specific immunotherapy.
自然变应原暴露、封闭抗体的诱导与特应性过敏的发生之间的关系——尤其是在存在IgE产生的情况下——存在争议。
阐明皮肤接触尘螨变应原的剂量与IgG产生相关的IgE介导的过敏反应易感性之间的关系。
将NC/Nga小鼠经皮暴露于不同剂量的屋尘螨变应原,以诱导特应性皮炎样皮肤病变。然后我们评估了皮肤病变、螨特异性免疫反应的诱导以及过敏反应的易感性。
观察到特应性皮炎样皮肤病变呈剂量依赖性加重,螨特异性IgG和IgE产生增加。然而,暴露于相对低剂量螨变应原的小鼠对螨变应原特异性过敏反应表现出高易感性。我们还表明,从Dp致敏小鼠中过继转移总IgG可使小鼠免于暴露于低剂量螨变应原时所见的高易感性。
高剂量经皮暴露于尘螨可诱导有效的封闭性IgG产生,即使伴有IgE产生。我们的数据可能支持这样一种观点,即IgG滴度升高而非IgE滴度降低是变应原特异性免疫治疗临床改善的标志。