Omalizumab-induced reductions in mast cell FcεRI expression and function
Omalizumab-induced reductions in mast cell FcεRI expression and function
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DOI：
10.1016/j.jaci.2004.06.032
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发表时间：
2004-09-01
影响因子：
14.2
通讯作者：
Saini, S
中科院分区：
文献类型：
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作者：
Beck, LA;Marcotte, GV;Saini, S
背景资料：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，组织中的肥大细胞同样改变FcepsilonRI的密度和function.Objective：我们研究了皮肤肥大细胞的表型转变平行的血液嗜碱性粒细胞在3个科目注入omalizumab.Methods：三个受试者过敏性鼻炎进行皮内皮肤试验滴定屋尘螨抗原在第0，7，70，196天omalizumab治疗。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。活检标本的特点是通过类胰蛋白酶和FcepsilonRI α免疫反应性，以及其他标志物（CD3，CD45 RO，CD68，皮肤淋巴细胞抗原，和主要碱性蛋白）的免疫化学方法。结果：奥马珠单抗收件人，但不是对照组，表现出减少FcepsilonRI α免疫反应性在第70和196天平行减少急性风团反应过敏原。然而，没有减少类胰蛋白酶阳性细胞，注意到在这些时间点。结论：奥马珠单抗的游离IgE水平的减少导致嗜碱性粒细胞FcephsilonRI受体表达的快速减少。相比之下，皮肤肥大细胞中Fc ε RI表达降低的时间过程较慢，并且与急性过敏原风团大小减小相关。
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 FcepsilonRI 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 FcepsilonRIalpha 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 FcepsilonRIalpha 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 FcepsilonRI receptor expression. In contrast, the time course for the decrease of FcepsilonRI expression in skin mast cells is slower and associated with decreased acute allergen wheal size.