Department of Dermatology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Clin Exp Immunol. 2014 Jun;176(3):310-9. doi: 10.1111/cei.12294.
Allergen-specific immunotherapy (SIT) is a clinically effective therapy for immunoglobulin (Ig)E-mediated allergic diseases. To reduce the risk of IgE-mediated side effects, chemically modified allergoids have been introduced. Furthermore, adsorbance of allergens to aluminium hydroxide (alum) is widely used to enhance the immune response. The mechanisms behind the adjuvant effect of alum are still not completely understood. In the present study we analysed the effects of alum-adsorbed allergens and allergoids on their immunogenicity in vitro and in vivo and their ability to activate basophils of allergic donors. Human monocyte derived dendritic cells (DC) were incubated with native Phleum pratense or Betula verrucosa allergen extract or formaldehyde- or glutaraldehyde-modified allergoids, adsorbed or unadsorbed to alum. After maturation, DC were co-cultivated with autologous CD4(+) T cells. Allergenicity was tested by leukotriene and histamine release of human basophils. Finally, in-vivo immunogenicity was analysed by IgG production of immunized mice. T cell proliferation as well as interleukin (IL)-4, IL-13, IL-10 and interferon (IFN)-γ production were strongly decreased using glutaraldehyde-modified allergoids, but did not differ between alum-adsorbed allergens or allergoids and the corresponding unadsorbed preparations. Glutaraldehyde modification also led to a decreased leukotriene and histamine release compared to native allergens, being further decreased by adsorption to alum. In vivo, immunogenicity was reduced for allergoids which could be partly restored by adsorption to alum. Our results suggest that adsorption of native allergens or modified allergoids to alum had no consistent adjuvant effect but led to a reduced allergenicity in vitro, while we observed an adjuvant effect regarding IgG production in vivo.
变应原特异性免疫治疗（SIT）是一种针对 IgE 介导的过敏性疾病的临床有效治疗方法。为了降低 IgE 介导的副作用风险，已经引入了化学修饰的变应原。此外，将变应原吸附到氢氧化铝（明矾）上广泛用于增强免疫反应。明矾佐剂作用的机制仍不完全清楚。在本研究中，我们分析了明矾吸附的变应原和变应原的体外和体内免疫原性及其激活过敏供体嗜碱性粒细胞的能力。将天然草属或桦属过敏原提取物或甲醛或戊二醛修饰的变应原吸附或未吸附到明矾上，与原代人单核细胞衍生的树突状细胞（DC）孵育。成熟后，DC 与自体 CD4+T 细胞共培养。通过人嗜碱性粒细胞的白三烯和组胺释放测试变应原性。最后，通过免疫接种小鼠的 IgG 产生分析体内免疫原性。使用戊二醛修饰的变应原，T 细胞增殖以及白细胞介素（IL）-4、IL-13、IL-10 和干扰素（IFN）-γ的产生均明显降低，但与吸附到明矾上的变应原或变应原之间无差异。戊二醛修饰还导致与天然变应原相比，白三烯和组胺的释放减少，而吸附到明矾上则进一步减少。在体内，变应原的免疫原性降低，这部分可以通过吸附到明矾上得到恢复。我们的结果表明，天然变应原或修饰变应原吸附到明矾上没有一致的佐剂作用，但在体外导致变应原性降低，而在体内观察到 IgG 产生的佐剂作用。
