Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge
Anti-IgE (omalizumab) inhibits late-phase reactions and inflammatory cells after repeat skin allergen challenge
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DOI：
10.1016/j.jaci.2005.05.035
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发表时间：
2005-09-01
影响因子：
14.2
通讯作者：
Kay, AB
中科院分区：
文献类型：
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作者：
Ong, YE;Menzies-Gow, A;Kay, AB
背景资料：抗IgE抗体（奥马珠单抗）可抑制早期和晚期哮喘反应以及基线时哮喘支气管活检组织中炎性细胞的浸润。慢性过敏原暴露对这些结果的影响尚不清楚。重复过敏原的挑战，在人类皮肤代表一个合适的模型来解决这个问题。目的：为了研究抗IgE（omalizumab）的早期阶段（EPR）和晚期阶段（LPR）的皮肤反应和细胞浸润的影响，通过使用重复皮肤过敏原的挑战，旨在模仿慢性过敏原exposition.Methods：24特应性过敏的志愿者接受omalizumab或安慰剂12周。过敏原（30个生物单位）和稀释剂对照的成对皮内激发以2周为间隔进行9次给药。早期和晚期皮肤反应和皮肤活检中的细胞浸润（使用免疫组织化学和原位杂交）进行了测量intervation.Results：与安慰剂相比，奥马珠单抗治疗的患者有一个渐进的减少LPR是显着大于其对EPR的影响（中位数，分别为-63%vs-24%; P = 0.009）。此外，与EPR的8周相比，LPR在开始治疗的2周内达到显著降低。在安慰剂组患者中，反复过敏原激发对嗜酸性粒细胞、中性粒细胞、T（H）2（CD 3（+）/IL-4（+））和总Fc γ RI+细胞的浸润有引发效应，而在接受奥马珠单抗的患者中，这种效应被消除。奥马珠单抗对LPR的更显著的作用和对几种炎性细胞类型的重复剂量引发效应的预防支持了奥马珠单抗抗的作用。慢性过敏性炎症相关疾病的IgE治疗。
Background: Anti-IgE (omalizumab) inhibited early and late asthmatic reactions and infiltration of inflammatory cells in asthmatic bronchial biopsies at baseline. The effect of chronic allergen exposure on these outcomes is unknown. Repeat allergen challenge in human skin represents a suitable model to address this question.Objective: To study the effect of anti-IgE (omalizumab) on early-phase (EPR) and late-phase (LPR) skin reactions and cellular infiltration by using a repeat skin allergen challenge designed to imitate chronic allergen exposure.Methods: Twenty-four atopic allergic volunteers received omalizumab or placebo for 12 weeks. Paired intradermal challenges of allergen (30 biological units) and diluent control were administered on 9 occasions at 2-week intervals. Early-phase and late-phase skin reactions and cellular infiltration in skin biopsies (using immunohistochemistry and in situ hybridization) were measured at intervals.Results: Compared with placebo, omalizumab-treated patients had a progressive reduction in the LPR that was significantly greater than its effect on the EPR (median, -63% vs -24% respectively; P = .009). In addition, significant reduction of the LPR was reached within 2 weeks of commencing treatment, compared with 8 weeks for the EPR. There was a priming effect of repeated allergen challenge on infiltration of eosinophil, neutrophil, T(H)2 (CD3(+)/IL-4(+)), and total Fc epsilon RI+ cells in patients on placebo that was abrogated in those receiving omalizumab.Conclusion: The more marked effect of omalizumab on the LPR and prevention of the repeat-dose priming effect on several inflammatory cell types support a role for anti-IgE treatment in conditions associated with chronic allergic inflammation.