Omalizumab-induced reductions in mast cell Fce psilon RI expression and function.
Omalizumab-induced reductions in mast cell Fce psilon RI expression and function.
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发表时间：
2004
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通讯作者：
L. Beck;G. V. Marcotte;D. MacGlashan;A. Togias;S. Saini
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作者：
L. Beck;G. V. Marcotte;D. MacGlashan;A. Togias;S. Saini
通过设计，奥马珠单抗结合循环中的游离IgE，并防止其附着于肥大细胞和嗜碱性粒细胞的表面，从而防止它们对过敏原作出反应。此前，奥马珠单抗快速降低游离IgE水平以及嗜碱性粒细胞高亲和力IgE受体，导致嗜碱性粒细胞介体对过敏原的反应显著降低。据推测，组织肥大细胞的Fc ε RI密度和功能也发生了类似的改变。目的：我们检测了3名接受奥马珠单抗治疗的受试者的皮肤肥大细胞和血液嗜碱性粒细胞的表型变化。方法3例变应性鼻炎患者在奥马珠单抗治疗的第0、7、70和196天接受了屋尘螨抗原皮内皮试滴定。作为对照受试者，在相似的时间点评价了5例未接受治疗的过敏性鼻炎受试者。所有受试者在18至24小时后在过敏原注射部位进行皮肤活检。活检标本通过类胰蛋白酶和Fc γ RI α免疫反应性以及其他标志物（CD 3、CD 45 RO、CD 68、皮肤淋巴细胞抗原和主要碱性蛋白）的免疫化学方法进行表征。结果Omalizumab接受者，而不是对照组，在第70天和第196天表现出Fc γ RI α免疫反应性的降低，与对变应原的急性风团反应的降低平行。然而，在这些时间点未观察到类胰蛋白酶阳性细胞减少。结论：奥马珠单抗降低游离IgE水平导致嗜碱性粒细胞Fc ε RI受体表达迅速降低。相比之下，皮肤肥大细胞中Fc ε RI表达降低的时间进程较慢，并与急性过敏原风团大小减少相关。
BACKGROUND By design, omalizumab binds free IgE in the circulation and prevents its attachment to the surface of mast cells and basophils, thereby preventing them from responding to allergens. Previously, omalizumab rapidly reduced free IgE levels, as well as basophil high-affinity IgE receptors, leading to significant reductions in basophil mediator response to allergen. It is assumed that tissue mast cells are similarly altered in their Fc epsilon RI density and function. OBJECTIVE We examined the phenotypic shift of skin mast cells in parallel to that of blood basophils in 3 subjects infused with omalizumab. METHODS Three subjects with allergic rhinitis underwent intradermal skin test titration with house dust mite antigen at days 0, 7, 70, and 196 of omalizumab treatment. As control subjects, 5 untreated subjects with allergic rhinitis were evaluated at similar time points. All subjects underwent skin biopsy 18 to 24 hours later at the site of allergen injection. Biopsy specimens were characterized by means of immunohistochemisty for tryptase and Fc epsilon RI alpha immunoreactivity, as well other markers (CD3, CD45RO, CD68, cutaneous lymphocyte antigen, and major basic protein). RESULTS Omalizumab recipients, but not control subjects, demonstrated reductions in Fc epsilon RI alpha immunoreactivity at days 70 and 196 in parallel with reductions in the acute wheal response to allergen. However, no reductions in tryptase-positive cells were noted at these time points. CONCLUSION Reductions in free IgE levels by omalizumab leads to a rapid reduction in basophil Fc epsilon RI receptor expression. In contrast, the time course for the decrease of Fc epsilon RI expression in skin mast cells is slower and associated with decreased acute allergen wheal size.