Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm, Sweden.
Allergy. 2011 Feb;66(2):255-63. doi: 10.1111/j.1398-9995.2010.02468.x. Epub 2010 Aug 30.
A hypoallergen of the major cat allergen Fel d 1, recombinant (r) Fel d 1 (DTE III), was previously shown to have retained T-cell reactivity and strongly reduced IgE-binding capacity compared to unmodified rFel d 1. Here, we evaluated the therapeutic capacity of rFel d 1 (DTE III) in a mouse model for cat allergy.
Mice were subcutaneously (s.c.) sensitized with rFel d 1 and subsequently treated (s.c.) with 50 or 200 μg rFel d 1 (DTE III), or 50 μg rFel d 1, prior to intranasal challenge with cat dander extract. Airway hyperreactivity (AHR), cells and cytokines in bronchoalveolar lavage fluid, splenocyte in vitro response, and serum immunoglobulins were analyzed. Seven cat-allergic patients and ten healthy controls were tested for skin prick test (SPT) reactivity to rFel d 1 (DTE III) and rFel d 1.
Mice treated with 50 and 200 μg rFel d 1 (DTE III), and 50 μg rFel d 1, produced increased serum levels of rFel d 1-specific IgG1 and IgG2a compared to sham-treated mice. IgG from all treatment groups could block binding of patients' IgE to rFel d 1. The 200 μg rFel d 1 (DTE III) treatment tended to reduce AHR. All mice tolerated treatment with rFel d 1 (DTE III), in contrast to only four of ten treated with rFel d 1. Compared to rFel d 1, the hypoallergen showed a tendency of reduced SPT reactivity.
The rFel d 1 (DTE III) hypoallergen might be a promising candidate for application in immunotherapy of cat allergy with improved safety and efficacy.
一种主要猫过敏原 Fel d 1 的低变应原,重组(r)Fel d 1(DTE III),与未修饰的 rFel d 1 相比,先前显示保留 T 细胞反应性,并且 IgE 结合能力大大降低。在这里,我们评估了 rFel d 1(DTE III)在猫过敏小鼠模型中的治疗能力。
用 rFel d 1 皮下(s.c.)致敏小鼠,然后用 50 或 200μg rFel d 1(DTE III),或 50μg rFel d 1 处理(s.c.),然后用猫皮屑提取物进行鼻内挑战。分析气道高反应性(AHR)、支气管肺泡灌洗液中的细胞和细胞因子、脾细胞体外反应和血清免疫球蛋白。对 7 名猫过敏患者和 10 名健康对照者进行 rFel d 1(DTE III)和 rFel d 1 的皮肤点刺试验(SPT)反应性测试。
用 50 和 200μg rFel d 1(DTE III)和 50μg rFel d 1 处理的小鼠产生了增加的 rFel d 1 特异性 IgG1 和 IgG2a 血清水平,与假处理的小鼠相比。所有治疗组的 IgG 均可阻断患者 IgE 与 rFel d 1 的结合。200μg rFel d 1(DTE III)治疗组趋向于降低 AHR。与仅 10 名接受 rFel d 1 治疗的患者中的 4 名相比,所有小鼠均耐受 rFel d 1(DTE III)的治疗。与 rFel d 1 相比,低变应原显示出 SPT 反应性降低的趋势。
rFel d 1(DTE III)低变应原可能是一种有前途的候选物,用于治疗猫过敏,具有改善的安全性和疗效。