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表皮免疫疗法可保护腰果致敏小鼠免于过敏反应。

Epicutaneous immunotherapy protects cashew-sensitized mice from anaphylaxis.

作者信息

Pelletier Benjamin, Perrin Audrey, Assoun Noémie, Plaquet Camille, Oreal Nathalie, Gaulme Laetitia, Bouzereau Adeline, Labernardière Jean-Louis, Ligouis Mélanie, Dioszeghy Vincent, Wavrin Sophie, Matthews Katie, Porcheray Fabrice, Sampson Hugh A, Hervé Pierre-Louis

机构信息

DBV Technologies, Montrouge, France.

DBV Technologies, New York, NY, USA.

出版信息

Allergy. 2021 Apr;76(4):1213-1222. doi: 10.1111/all.14605. Epub 2020 Oct 23.

DOI:10.1111/all.14605
PMID:32996148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8246921/
Abstract

BACKGROUND

The prevalence of tree nut allergy has increased worldwide, and cashew has become one of the most common food allergens. More critically, cashew allergy is frequently associated with severe anaphylaxis. Despite the high medical need, no approved treatment is available and strict avoidance and preparedness for prompt treatment of allergic reactions are considered dual standard of care. In the meantime, Phase III study results suggest investigational epicutaneous immunotherapy (EPIT) may be a relevant and safe treatment for peanut allergy and may improve the quality of life for many peanut allergic children.

OBJECTIVE

We aimed to evaluate the capacity of EPIT to provide protection against cashew-induced anaphylaxis in a relevant mouse model.

METHODS

The efficacy of EPIT was evaluated by applying patches containing cashew allergens to cashew-sensitized mice. As negative control, sham mice received patches containing excipient. Following treatment, mice were challenged orally to cashew and anaphylactic symptoms, as well as plasmatic levels of mast-cell proteases (mMCP)-1/7, were quantified.

RESULTS

Of 16 weeks of EPIT significantly protects against anaphylaxis by promoting a faster recovery of challenged mice. This protection was characterized by a significant reduction of temperature drop and clinical symptoms, 60 minutes after challenge. This was associated with a decrease in mast-cell reactivity as attested by the reduction of mMCP-1/7 in plasma, suggesting that EPIT specifically decrease IgE-mediated anaphylaxis.

CONCLUSION

We demonstrate that EPIT markedly reduced IgE-mediated allergic reactions in a mouse model of cashew allergy, which suggests that EPIT may be a relevant approach to treating cashew allergy.

摘要

背景

全球范围内,对坚果过敏的患病率呈上升趋势,腰果已成为最常见的食物过敏原之一。更关键的是,腰果过敏常与严重过敏反应相关。尽管医疗需求迫切,但目前尚无获批的治疗方法,严格避免接触并随时准备应对过敏反应被视为双重标准的治疗措施。与此同时,III期研究结果表明,试验性的经皮免疫疗法(EPIT)可能是一种针对花生过敏的有效且安全的治疗方法,并且可能改善许多花生过敏儿童的生活质量。

目的

我们旨在评估EPIT在相关小鼠模型中预防腰果诱发过敏反应的能力。

方法

通过向对腰果致敏的小鼠贴敷含腰果过敏原的贴片来评估EPIT的疗效。作为阴性对照,假处理小鼠接受含赋形剂的贴片。处理后,给小鼠口服腰果进行激发试验,并对过敏症状以及肥大细胞蛋白酶(mMCP)-1/7的血浆水平进行定量分析。

结果

16周的EPIT通过促进激发试验后小鼠更快恢复,显著预防了过敏反应。这种保护作用表现为激发试验60分钟后体温下降和临床症状显著减轻。这与血浆中mMCP-1/7的减少所证明的肥大细胞反应性降低相关,表明EPIT特异性降低了IgE介导的过敏反应。

结论

我们证明,在腰果过敏小鼠模型中,EPIT显著降低了IgE介导的过敏反应,这表明EPIT可能是一种治疗腰果过敏的有效方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/885f60a5344c/ALL-76-1213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/b3c38c37d4fd/ALL-76-1213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/404b8ae183be/ALL-76-1213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/3cd0c9113f72/ALL-76-1213-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/bca07bed0955/ALL-76-1213-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/f6f765846d11/ALL-76-1213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/885f60a5344c/ALL-76-1213-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/b3c38c37d4fd/ALL-76-1213-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/404b8ae183be/ALL-76-1213-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/3cd0c9113f72/ALL-76-1213-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/bca07bed0955/ALL-76-1213-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/f6f765846d11/ALL-76-1213-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c26e/8246921/885f60a5344c/ALL-76-1213-g001.jpg

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