原標(biāo)題：伴鼻息肉慢性鼻竇炎中Dupilumab可減輕局部2型促炎生物標(biāo)志物
背景：伴鼻息肉慢性鼻竇炎（CRSwNP）是2型介導(dǎo)的炎癥性疾病，該類疾病與重要的臨床、社會(huì)和經(jīng)濟(jì)負(fù)擔(dān)以及難以滿足的治療需求相關(guān)。靶向結(jié)合人白介素4受體α（IL-4Rα）亞基的全人單克隆抗體Dupilumab在CRSwNP和其他2型疾?。ㄈ缣貞?yīng)性皮炎和哮喘）中顯示出治療效果和可接受的安全性?，F(xiàn)在，我們通過(guò)一項(xiàng)隨機(jī)且有安慰劑作為對(duì)照的2期臨床試驗(yàn)，報(bào)告了Dupilumab對(duì)CRSwNP患者鼻分泌物和鼻息肉組織中2型炎癥生物標(biāo)記物的局部作用。
方法：CRSwNP患者采用每周300 mg Dupilumab或安慰劑治療16周后，通過(guò)免疫測(cè)定技術(shù)測(cè)量其鼻分泌物和鼻息肉組織勻漿中的細(xì)胞因子、趨化因子和總免疫球蛋白E（IgE）的水平。
結(jié)果：與eotaxin-3安慰劑（-30.06 vs -0.86 pg / mL; P = 0.0008）和總IgE（-7.90對(duì)-1.86 IU / mL；P = 0.022）相比，Dupilumab治療后鼻分泌物中2型生物標(biāo)志物的濃度（0~16周最小二乘均值的曲線下面積相對(duì)于基線的變化）有所降低。與基線相比，Dupilumab治療還降低了第16周鼻息肉組織中2型生物標(biāo)志物的水平，如嗜酸性陽(yáng)離子蛋白（P = 0.008），eotaxin-2（P = 0.008），eotaxin-3（P = 0.031），肺和活化調(diào)節(jié)趨化因子（P = 0.016），IgE（P = 0.023）和IL-13（P = 0.031）。
結(jié)論：Dupilumab治療減少了CRSwNP患者鼻分泌物和鼻息肉組織中2型炎癥的多種生物標(biāo)志物，表明IL-4Rα信號(hào)的拮抗作用抑制了IL-4或IL-13依賴性過(guò)程，例如粘膜IgE的形成以及趨化因子的表達(dá)將炎癥細(xì)胞吸引到鼻粘膜。
延伸閱讀
Allergy                                                   
Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis
DOI: 10.1111/all.13685
Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2-mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo-controlled, phase 2 trial
Methods: Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks.
Results: With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin-3 (-30.06 vs -0.86 pg/mL; P = 0.0008) and total IgE (-7.90 vs -1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin-2 (P = 0.008), eotaxin-3 (P = 0.031), pulmonary and activation-regulated chemokine (P = 0.016), IgE (P = 0.023), and IL-13 (P = 0.031).
Conclusion: Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL-4Rα signaling suppresses IL-4-/IL-13-dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
Author:
Karin Jonstam
Correspondence:
Brian N Swanson, Leda P Mannent, Lars-Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D Hamilton, Annette Grabher, Neil M H Graham, Gianluca Pirozzi, Claus Bachert.
All Author:
Karin Jonstam, Brian N Swanson, Leda P Mannent, Lars-Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D Hamilton, Annette Grabher, Neil M H Graham, Gianluca Pirozzi, Claus Bachert.
2019-1-21 Article 
　　創(chuàng)建過(guò)敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過(guò)敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。