奥马珠单抗治疗期间FcepsilonRI介导的人嗜碱性粒细胞促哮喘细胞因子和炎症趋化因子释放下降
2010/02/23
背景：采用人化IgE清除抗体-奥马珠单抗（rhuMAb-E25, Xolair(R)）治疗哮喘能减少气道炎症和哮喘症状。前期研究显示，奥马珠单抗可导致哮喘患者外周血嗜碱性粒细胞表面高亲和力IgE受体（FcepsilonRI）显著且可逆性下降。受体表达降低对FcepsilonRI 介导的参与过敏性哮喘的细胞因子的合成和释放的影响尚未有研究。
方法：15例哮喘志愿者接受为期12周的奥马珠单抗治疗。于治疗前、治疗期间、治疗后2周和6个月分离患者外周血嗜碱性粒细胞。嗜碱性粒细胞用于分析基线和抗IgE抗体刺激后细胞因子、趋化因子及组胺的释放。数据集采用重复测量单因素方差分析和配对t检验。
结果：抗IgE刺激能诱导人嗜碱性粒细胞合成，以及Th2细胞因子（IL-4和IL-13）和趋化因子（IL-8和RANTES）的释放。奥马珠单抗治疗期间抗IgE刺激释放的IL-4、IL-13和IL-8显著下降，并在奥马珠单抗撤药后能恢复至治疗前水平。奥马珠单抗不会改变嗜碱性粒细胞组胺水平，以及基线和抗IgE刺激后组胺的释放。
结论：奥马珠单抗可能部分通过抑制FcepsilonRI介导的嗜碱性粒细胞Th2细胞因子及某些趋化因子的生成作用减少哮喘症状。由于奥马珠单抗治疗后FcepsilonRI丧失，抗IgE刺激诱导的嗜碱性粒细胞细胞因子合成的敏感性强于组胺释放。
（苏楠 审校）
Int Arch Allergy Immunol. 2009 Oct 22;151(4):275-284.
Reduced FcepsilonRI-Mediated Release of Asthma-Promoting Cytokines and Chemokines from Human Basophils during Omalizumab Therapy.
Oliver JM, Tarleton CA, Gilmartin L, Archibeque T, Qualls CR, Diehl L, Wilson BS, Schuyler M.
Background: Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair(R)), reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined.
Methods: Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests.
Results: Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release.
Conclusions: Omalizumab may reduce asthma symptoms in part by suppressing the FcepsilonRI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of FcepsilonRI caused by omalizumab treatment.
Int Arch Allergy Immunol. 2009 Oct 22;151(4):275-284.
方法：15例哮喘志愿者接受为期12周的奥马珠单抗治疗。于治疗前、治疗期间、治疗后2周和6个月分离患者外周血嗜碱性粒细胞。嗜碱性粒细胞用于分析基线和抗IgE抗体刺激后细胞因子、趋化因子及组胺的释放。数据集采用重复测量单因素方差分析和配对t检验。
结果：抗IgE刺激能诱导人嗜碱性粒细胞合成，以及Th2细胞因子（IL-4和IL-13）和趋化因子（IL-8和RANTES）的释放。奥马珠单抗治疗期间抗IgE刺激释放的IL-4、IL-13和IL-8显著下降，并在奥马珠单抗撤药后能恢复至治疗前水平。奥马珠单抗不会改变嗜碱性粒细胞组胺水平，以及基线和抗IgE刺激后组胺的释放。
结论：奥马珠单抗可能部分通过抑制FcepsilonRI介导的嗜碱性粒细胞Th2细胞因子及某些趋化因子的生成作用减少哮喘症状。由于奥马珠单抗治疗后FcepsilonRI丧失，抗IgE刺激诱导的嗜碱性粒细胞细胞因子合成的敏感性强于组胺释放。
（苏楠 审校）
Int Arch Allergy Immunol. 2009 Oct 22;151(4):275-284.
Reduced FcepsilonRI-Mediated Release of Asthma-Promoting Cytokines and Chemokines from Human Basophils during Omalizumab Therapy.
Oliver JM, Tarleton CA, Gilmartin L, Archibeque T, Qualls CR, Diehl L, Wilson BS, Schuyler M.
Background: Treating asthmatics with the humanized IgE-scavenging antibody, omalizumab (rhuMAb-E25, Xolair(R)), reduces airways inflammation and asthma symptoms. Previously, omalizumab was shown to cause a dramatic and reversible loss of cell surface high-affinity IgE receptors, FcepsilonRI, from the peripheral blood basophils of asthmatics. The consequences of receptor loss for the FcepsilonRI-mediated synthesis and release of cytokines implicated in allergic asthma have not been examined.
Methods: Fifteen asthmatic volunteers each received omalizumab for 12 weeks. Peripheral blood basophils were isolated before, during, 2 weeks after and 6 months after omalizumab. Basophils were assayed for the basal and anti-IgE-stimulated release of cytokines, chemokines and histamine. Pooled data were analyzed by repeated measures ANOVA and by paired t tests.
Results: Anti-IgE-stimulated human basophils synthesize and release Th2 cytokines (IL-4, IL-13) and chemokines (IL-8, RANTES). The anti-IgE-stimulated release of IL-4, IL-13 and IL-8 was reduced during omalizumab treatment and returned to pretreatment levels after omalizumab withdrawal. Omalizumab did not alter basophil histamine levels or basal and anti-IgE-stimulated histamine release.
Conclusions: Omalizumab may reduce asthma symptoms in part by suppressing the FcepsilonRI-mediated production by basophils of Th2 cytokines and selected chemokines. Anti-IgE-stimulated basophil cytokine synthesis appears more sensitive than histamine release to the loss of FcepsilonRI caused by omalizumab treatment.
Int Arch Allergy Immunol. 2009 Oct 22;151(4):275-284.
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