Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma
Effects of treatment with anti-immunoglobulin E antibody omalizumab on airway inflammation in allergic asthma
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DOI：
10.1164/rccm.200312-1651oc
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发表时间：
2004-09-15
影响因子：
24.7
通讯作者：
Fahy, JV
中科院分区：
文献类型：
--
作者：
Djukanovic, R;Wilson, SJ;Fahy, JV
IgE在过敏性哮喘中起重要作用。我们假设降低气道粘膜中的IgE可以减轻气道炎症。45例痰嗜酸性粒细胞增多2%或以上的轻中度持续性哮喘患者接受抗IgE人源化单克隆抗体（奥马珠单抗）（n = 22）或安慰剂（n = 23）治疗16周。结果包括诱导痰和支气管活检中的炎性细胞和乙酰甲胆碱反应性。奥马珠单抗治疗导致血清IgE显著降低，气道粘膜中IgE（+）细胞减少。奥马珠单抗组的平均痰嗜酸性粒细胞计数百分比从6.6%显著下降（p < 0.001）至1.7%，降幅显著（p = 0.05）大于安慰剂组（8.5%至7.0%）。这与组织嗜酸性粒细胞、IgE高亲和力Fc受体阳性细胞、CD 3（+）、CD 4（+）和CD 8（+）T淋巴细胞、B淋巴细胞和白细胞介素-4染色细胞显著减少相关，但与乙酰甲胆碱气道高反应性改善无关。这项研究显示了奥马珠单抗治疗的副作用，并为奥马珠单抗减少哮喘急性发作和更严重哮喘的其他哮喘结局的机制提供了线索。奥马珠单抗对乙酰甲胆碱反应性缺乏影响表明，IgE或嗜酸性粒细胞可能与轻度至中度哮喘患者对乙酰甲胆碱的气道高反应性无因果关系。
IgE plays an important role in allergic asthma. We hypothesized that reducing IgE in the airway mucosa would reduce airway inflammation. Forty-five patients with mild to moderate persistent asthma with sputum eosinophilia of 2% or more were treated with humanized monoclonal antibody against IgE (omalizumab) (n = 22) or placebo (n = 23) for 16 weeks. Outcomes included inflammatory cells in induced sputum and bronchial biopsies, and methacholine responsiveness. Treatment with omalizumab resulted in marked reduction of serum IgE and a reduction of IgE(+) cells in the airway mucosa. The mean percentage sputum eosinophil count decreased significantly (p < 0.001) from 6.6 to 1.7% in the omalizumab group, a reduction significantly (p = 0.05) greater than with placebo (8.5 to 7.0%). This was associated with a significant reduction in tissue eosinophils; cells positive for the high-affinity Fc receptor for IgE; CD3(+), CD4(+), and CD8(+) T lymphocytes; B lymphocytes; and cells staining for interleukin-4, but not with improvement in airway hyperresponsiveness to methacholine. This study shows antiinflammatory effects of omalizumab treatment and provides clues for mechanisms whereby omalizumab reduces asthma exacerbations and other asthma outcomes in more severe asthma. The lack of effect of omalizumab on methacholine responsiveness suggests that IgE or eosinophils may not be causally linked to airway hyperresponsiveness to methacholine in mild to moderate asthma.