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奥马珠单抗在过敏性疾病中的抗免疫球蛋白E治疗:抗炎活性和临床疗效的最新进展

Anti-immunoglobulin E treatment with omalizumab in allergic diseases: an update on anti-inflammatory activity and clinical efficacy.

作者信息

Holgate S T, Djukanović R, Casale T, Bousquet J

机构信息

Southampton General Hospital, Southampton, UK.

出版信息

Clin Exp Allergy. 2005 Apr;35(4):408-16. doi: 10.1111/j.1365-2222.2005.02191.x.

Abstract

Omalizumab is a humanized monoclonal anti-IgE antibody developed for the treatment of allergic disease, with established efficacy in patients with moderate-to-severe allergic asthma and in patients with intermittent (seasonal) and persistent (perennial) allergic rhinitis (AR). Omalizumab is known to result in a marked reduction in serum levels of free IgE and down-regulation of IgE receptors on circulating basophils. Recent work has shed further light on its mechanism of action, showing significant and profound reductions in tissue (nasal and bronchial) eosinophils and in bronchial IgE+ cells (mast cells), as well as T cells and B cells. Omalizumab treatment was also shown to be associated with down-regulation of IgE receptors on circulating (precursor) dendritic cells, suggesting that blocking IgE may inhibit more chronic aspects of allergic inflammation involving T cell activation. Further work with omalizumab demonstrated it to have important benefits in patients with poorly controlled asthma despite high-dose inhaled corticosteroid therapy, and analysis of clinical data suggests that the patients who are the best 'responders' to anti-IgE treatment are those with asthma at the more severe end of the spectrum. Notably, systemic anti-IgE therapy with omalizumab has been shown to improve symptoms, quality of life and disease control (asthma exacerbations) in patients with concomitant asthma and persistent AR. These impressive clinical data and the studies elucidating the anti-inflammatory profile of omalizumab also serve to emphasize the fundamental importance of IgE in the pathogenesis of allergic diseases.

摘要

奥马珠单抗是一种开发用于治疗过敏性疾病的人源化单克隆抗IgE抗体,对中重度过敏性哮喘患者以及间歇性(季节性)和持续性(常年性)过敏性鼻炎(AR)患者具有既定疗效。已知奥马珠单抗可显著降低血清游离IgE水平,并下调循环嗜碱性粒细胞上的IgE受体。最近的研究进一步揭示了其作用机制,显示组织(鼻腔和支气管)嗜酸性粒细胞、支气管IgE+细胞(肥大细胞)以及T细胞和B细胞显著且大幅减少。奥马珠单抗治疗还显示与循环(前体)树突状细胞上的IgE受体下调有关,这表明阻断IgE可能抑制涉及T细胞活化的过敏性炎症的更多慢性方面。对奥马珠单抗的进一步研究表明,尽管使用了高剂量吸入性糖皮质激素治疗,但它对哮喘控制不佳的患者仍有重要益处,临床数据分析表明,对抗IgE治疗反应最佳的患者是哮喘病情更严重的患者。值得注意的是,使用奥马珠单抗进行全身抗IgE治疗已被证明可改善合并哮喘和持续性AR患者的症状、生活质量和疾病控制(哮喘发作)。这些令人印象深刻的临床数据以及阐明奥马珠单抗抗炎特性的研究也强调了IgE在过敏性疾病发病机制中的根本重要性。

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