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嗜酸性粒细胞在马的复发性荨麻疹中发挥着惊人的主导作用。

Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses.

作者信息

Birkmann Katharina, Jebbawi Fadi, Waldern Nina, Hug Sophie, Inversini Victoria, Keller Giulia, Holm Anja, Grest Paula, Canonica Fabia, Schmid-Grendelmeier Peter, Fettelschoss-Gabriel Antonia

机构信息

Evax AG, Im Binz 3, 8357 Guntershausen, Switzerland.

Equine Department, Veterinary Faculty, Ludwig Maximilians University Munich LMU, Sonnenstrasse 14, 85764 Oberschleißheim, Germany.

出版信息

Vaccines (Basel). 2024 May 21;12(6):562. doi: 10.3390/vaccines12060562.

DOI:10.3390/vaccines12060562
PMID:38932291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11209473/
Abstract

Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids.

摘要

荨麻疹,无论是否与过敏相关,在马匹中都很常见,且复发率往往很高。管理这些马匹令人沮丧,而且缺乏有效的治疗方案。在一项针对受昆虫叮咬超敏反应影响的马匹使用靶向嗜酸性粒细胞的eIL-5-CuMV-TT疫苗的研究中,由于一个偶然发现,我们观察到在随后四年通过再次接种疫苗预防了季节性荨麻疹的复发。在一个关于非季节性荨麻疹马匹的探索性病例系列中,我们旨在研究嗜酸性粒细胞在荨麻疹中的作用。进行了皮肤打孔活检以进行组织学检查和嗜酸性粒细胞相关基因的qPCR检测。此外,对两匹严重的、非季节性的、复发性荨麻疹马匹使用eIL-5-CuMV-TT进行接种,并通过再次接种疫苗对荨麻疹发作情况进行了数年的随访。嗜酸性粒细胞趋化因子-2、嗜酸性粒细胞趋化因子-3、白细胞介素-5、C-C趋化因子受体5和CXC趋化因子配体10对荨麻疹病变表现出高敏感性和特异性,而在50%的组织学切片中存在嗜酸性粒细胞。eIL-5-CuMV-TT疫苗降低了血液中的嗜酸性粒细胞计数,消除了荨麻疹的临床症状,甚至预防了非季节性复发性荨麻疹马匹出现新的荨麻疹发作。这表明嗜酸性粒细胞在马匹荨麻疹中起主导作用,靶向嗜酸性粒细胞提供了一种有吸引力的新治疗选择,可取代皮质类固醇的使用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/262ed41a26d0/vaccines-12-00562-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/086f16f0b5c3/vaccines-12-00562-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/ae9d6261b093/vaccines-12-00562-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/221dad787799/vaccines-12-00562-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/262ed41a26d0/vaccines-12-00562-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/086f16f0b5c3/vaccines-12-00562-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/ae9d6261b093/vaccines-12-00562-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/221dad787799/vaccines-12-00562-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4176/11209473/262ed41a26d0/vaccines-12-00562-g004.jpg

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本文引用的文献

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Benralizumab does not elicit therapeutic effect in patients with chronic spontaneous urticaria: results from the phase IIb multinational randomized double-blind placebo-controlled ARROYO trial.贝那鲁肽在慢性自发性荨麻疹患者中没有疗效:来自 IIb 期多国随机双盲安慰剂对照 ARROYO 试验的结果。
Br J Dermatol. 2024 Jul 16;191(2):187-199. doi: 10.1093/bjd/ljae067.
2
Mepolizumab incompletely suppresses clinical flares in a pilot study of episodic angioedema with eosinophilia.在一项嗜酸性粒细胞增多性发作性血管性水肿的初步研究中,美泊利单抗不能完全抑制临床发作。
J Allergy Clin Immunol. 2024 Mar;153(3):821-830.e6. doi: 10.1016/j.jaci.2023.11.002. Epub 2023 Nov 10.
3
Targeting eosinophils by active vaccination against interleukin-5 reduces basophil counts in horses with insect bite hypersensitivity in the 2nd year of vaccination.
通过针对白细胞介素-5 的主动免疫接种靶向嗜酸性粒细胞,可降低第 2 年接种疫苗时昆虫叮咬过敏马的嗜碱性粒细胞计数。
Vet J. 2022 Oct;288:105896. doi: 10.1016/j.tvjl.2022.105896. Epub 2022 Sep 17.
4
Living without eosinophils: evidence from mouse and man.没有嗜酸性粒细胞也能存活:来自小鼠和人类的证据。
Eur Respir J. 2023 Jan 12;61(1). doi: 10.1183/13993003.01217-2022. Print 2023 Jan.
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The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria.国际 EAACI/GA²LEN/EuroGuiDerm/APAAACI 荨麻疹定义、分类、诊断和管理指南。
Allergy. 2022 Mar;77(3):734-766. doi: 10.1111/all.15090. Epub 2021 Oct 20.
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The Enigma of Eosinophil Degranulation.嗜酸性粒细胞脱颗粒之谜。
Int J Mol Sci. 2021 Jun 30;22(13):7091. doi: 10.3390/ijms22137091.
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Eosinophil-mast cell interaction: Mepolizumab leads to a reduction of clinical symptoms and serum tryptase in a patient with eosinophilic asthma and idiopathic mast cell activation.嗜酸性粒细胞-肥大细胞相互作用:美泊利珠单抗可使一名患有嗜酸性粒细胞性哮喘和特发性肥大细胞活化的患者的临床症状和血清类胰蛋白酶降低。
J Allergy Clin Immunol Pract. 2021 Mar;9(3):1393-1395.e1. doi: 10.1016/j.jaip.2020.10.020. Epub 2020 Oct 20.
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Allergy. 2020 Apr;75(4):862-871. doi: 10.1111/all.14145. Epub 2020 Feb 6.