慢性自发性荨麻疹发病过程中肥大细胞作用及其靶向治疗进展

doi:10.35541/cjd.20240291

中华皮肤科杂志 ›› 2024, e20240291.doi: 10.35541/cjd.20240291

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慢性自发性荨麻疹发病过程中肥大细胞作用及其靶向治疗进展

许焯红¹ 周栩悦¹ 胡煜² 顾恒²

¹北京协和医学院中国医学科学院皮肤病医院皮肤病研究所，南京 210042；²中国医学科学院北京协和医学院皮肤病医院，南京 210042

收稿日期:2024-05-30 修回日期:2024-10-31 发布日期:2024-12-09
通讯作者: 胡煜;顾恒 E-mail:huyupumc@126.com; guheng@aliyun.com
基金资助:
国家自然科学基金（82273552、82203947、82304049）；中国医学科学院医学与健康科技创新工程（CIFMS-2021-I2M-1-001）；2023年北京协和医学院中央高校基本科研业务费（3332023172）

Role of mast cells in the pathogenesis of chronic spontaneous urticaria and advances in mast cell-targeted therapies

Xu Zhuohong¹, Zhou Xuyue¹, Hu Yu², Gu Heng²

¹Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences ＆ Peking Union Medical College, Nanjing 210042, China; ²Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China

Received:2024-05-30 Revised:2024-10-31 Published:2024-12-09
Contact: Hu Yu; Gu Heng E-mail:huyupumc@126.com; guheng@aliyun.com
Supported by:
National Natural Science Foundation of China （82273552, 82203947, 82304049）; CAMS Innovation Fund for Medical Sciences （CIFMS-2021-I2M-1-001）; Fundamental Research Funds for the Central Universities （3332023172）

摘要/Abstract

摘要： 【摘要】慢性自发性荨麻疹（CSU）是一种主要由肥大细胞驱动的常见皮肤疾病，肥大细胞主要通过Ⅰ型和Ⅱb型自身免疫反应在CSU的发展中发挥作用。本文综述肥大细胞在CSU中的作用机制、靶向肥大细胞治疗CSU的新方法以及未来的研究方向，为临床治疗提供参考。

关键词: 慢性荨麻疹, 肥大细胞, 自身免疫, 抗体, 单克隆, 治疗, 临床研究性, 小分子药物

Abstract: 【Abstract】 Chronic spontaneous urticaria （CSU） is a common skin disorder primarily driven by mast cells. It has been found that mast cells play a crucial role in the development of CSU mainly through type Ⅰ and Ⅱb autoimmune responses. This review summarizes the mechanisms of action of mast cells in CSU, new methods of targeting mast cells for the treatment of CSU, and future research directions, providing a reference for the clinical treatment of CSU.

Key words: Chronic urticaria, Mast cells, Autoimmunity, Antibodies, monoclonal, Therapies, investigational, Small molecule drug

许焯红周栩悦胡煜顾恒. 慢性自发性荨麻疹发病过程中肥大细胞作用及其靶向治疗进展[J]. 中华皮肤科杂志, 2024,e20240291. doi:10.35541/cjd.20240291

Xu Zhuohong, Zhou Xuyue, Hu Yu, Gu Heng. Role of mast cells in the pathogenesis of chronic spontaneous urticaria and advances in mast cell-targeted therapies[J]. Chinese Journal of Dermatology,2024,e20240291. doi:10.35541/cjd.20240291

参考文献 42

［1］	Kolkhir P, Church MK, Weller K, et al. Autoimmune chronic spontaneous urticaria: what we know and what we do not know［J］. J Allergy Clin Immunol, 2017,139（6）:1772⁃1781.e1. doi: 10.1016/j.jaci.2016.08.050.
［2］	Dobrican CT, Muntean IA, Pintea I, et al. Immunological signature of chronic spontaneous urticaria （review）［J］. Exp Ther Med, 2022,23（6）:381. doi: 10.3892/etm.2022.11309.
［3］	Nakano N, Kitaura J. Mucosal mast cells as key effector cells in food allergies［J］. Cells, 2022,11（3）:329. doi: 10.3390/cells 11030329.
［4］	Reber LL, Sibilano R, Mukai K, et al. Potential effector and immunoregulatory functions of mast cells in mucosal immunity［J］. Mucosal Immunol, 2015,8（3）:444⁃463. doi: 10.1038/mi. 2014.131.
［5］	Elieh⁃Ali⁃Komi D, Metz M, Kolkhir P, et al. Chronic urticaria and the pathogenic role of mast cells［J］. Allergol Int, 2023,72（3）:359⁃368. doi: 10.1016/j.alit.2023.05.003.
［6］	Schmetzer O, Lakin E, Topal FA, et al. IL⁃24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria［J］. J Allergy Clin Immunol, 2018,142（3）:876⁃882. doi: 10.1016/j.jaci.2017.10.035.
［7］	Kolkhir P, Muñoz M, Asero R, et al. Autoimmune chronic spontaneous urticaria［J］. J Allergy Clin Immunol, 2022,149（6）:1819⁃1831. doi: 10.1016/j.jaci.2022.04.010.
［8］	Nagata Y, Suzuki R. FcεRI: a master regulator of mast cell functions［J］. Cells, 2022,11（4）:622. doi: 10.3390/cells1104 0622.
［9］	Kaplan A, Lebwohl M, Giménez⁃Arnau AM, et al. Chronic spontaneous urticaria: focus on pathophysiology to unlock treatment advances［J］. Allergy, 2023,78（2）:389⁃401. doi: 10. 1111/all.15603.
［10］	Hide M, Francis DM, Grattan CE, et al. Autoantibodies against the high⁃affinity IgE receptor as a cause of histamine release in chronic urticaria［J］. N Engl J Med, 1993,328（22）:1599⁃1604. doi: 10.1056/NEJM199306033282204.
［11］	Asero R, Marzano AV, Ferrucci S, et al. Co⁃occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria［J］. Clin Exp Immunol, 2020,200（3）:242⁃249. doi: 10. 1111/cei.13428.
［12］	中华医学会皮肤性病学分会荨麻疹研究中心. 中国荨麻疹诊疗指南（2022版）［J］. 中华皮肤科杂志, 2022,55（12）:1041⁃1049. doi: 10.35541/cjd.20220609.
［13］	Maurer M, Rosén K, Hsieh HJ, et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria［J］. N Engl J Med, 2013,368（10）:924⁃935. doi: 10.1056/NEJMoa 1215372.
［14］	Thomas D, McDonald VM, Stevens S, et al. Biologics （mepolizumab and omalizumab） induced remission in severe asthma patients［J］. Allergy, 2024,79（2）:384⁃392. doi: 10.1111/all.15867.
［15］	Yuan W, Hu S, Li M, et al. Efficacy and safety of omalizumab in Chinese patients with anti⁃histamine refractory chronic spontaneous urticaria［J］. Dermatol Ther, 2022,35（4）:e15303. doi: 10.1111/dth.15303.
［16］	Gasser P, Tarchevskaya SS, Guntern P, et al. The mechanistic and functional profile of the therapeutic anti⁃IgE antibody ligelizumab differs from omalizumab［J］. Nat Commun, 2020,11（1）:165. doi: 10.1038/s41467⁃019⁃13815⁃w.
［17］	Maurer M, Giménez⁃Arnau AM, Sussman G, et al. Ligelizumab for chronic spontaneous urticaria［J］. N Engl J Med, 2019,381（14）:1321⁃1332. doi: 10.1056/NEJMoa1900408.
［18］	Kuo BS, Li CH, Chen JB, et al. IgE⁃neutralizing UB⁃221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23⁃mediated IgE downregulation and relieves urticaria symptoms［J］. J Clin Invest, 2022,132（15）:e157765. doi: 10.1172/JCI 157765.
［19］	Johal KJ, Saini SS. Current and emerging treatments for chronic spontaneous urticaria［J］. Ann Allergy Asthma Immunol, 2020,125（4）:380⁃387. doi: 10.1016/j.anai.2019.08.465.
［20］	Ramirez Molina C, Falkencrone S, Skov PS, et al. GSK2646264, a spleen tyrosine kinase inhibitor, attenuates the release of histamine in ex vivo human skin［J］. Br J Pharmacol, 2019,176（8）:1135⁃1142. doi: 10.1111/bph.14610.
［21］	Metz M, Sussman G, Gagnon R, et al. Fenebrutinib in H1 antihistamine⁃refractory chronic spontaneous urticaria: a randomized phase 2 trial［J］. Nat Med, 2021,27（11）:1961⁃1969. doi: 10.1038/s41591⁃021⁃01537⁃w.
［22］	Maurer M, Berger W, Giménez⁃Arnau A, et al. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria［J］. J Allergy Clin Immunol, 2022,150（6）:1498⁃1506.e2. doi: 10.1016/j.jaci.2022.08.027.
［23］	Jain V, Giménez⁃Arnau A, Hayama K, et al. Remibrutinib demonstrates favorable safety profile and sustained efficacy in chronic spontaneous urticaria over 52 weeks［J］. J Allergy Clin Immunol, 2024,153（2）:479⁃486.e4. doi: 10.1016/j.jaci.2023. 10.007.
［24］	Morales JK, Falanga YT, Depcrynski A, et al. Mast cell homeostasis and the JAK⁃STAT pathway［J］. Genes Immun, 2010,11（8）:599⁃608. doi: 10.1038/gene.2010.35.
［25］	Clauzure M, Táquez Delgado MA, Phillip JM, et al. Histamine H4 receptor agonism induces antitumor effects in human T⁃cell lymphoma［J］. Int J Mol Sci, 2022,23（3）:1378. doi: 10.3390/ijms23031378.
［26］	Murata Y, Song M, Kikuchi H, et al. Phase 2a, randomized, double⁃blind, placebo⁃controlled, multicenter, parallel⁃group study of a H4 R⁃antagonist （JNJ⁃39758979） in Japanese adults with moderate atopic dermatitis［J］. J Dermatol, 2015,42（2）:129⁃139. doi: 10.1111/1346⁃8138.12726.
［27］	Kollmeier AP, Barnathan ES, O'Brien C, et al. A phase 2a study of toreforant, a histamine H4 receptor antagonist, in eosinophilic asthma［J］. Ann Allergy Asthma Immunol, 2018,121（5）:568⁃574. doi: 10.1016/j.anai.2018.08.001.
［28］	Werfel T, Layton G, Yeadon M, et al. Efficacy and safety of the histamine H4 receptor antagonist ZPL⁃3893787 in patients with atopic dermatitis［J］. J Allergy Clin Immunol, 2019,143（5）:1830⁃1837.e4. doi: 10.1016/j.jaci.2018.07.047.
［29］	Oliver ET, Chichester K, Devine K, et al. Effects of an oral CRTh2 antagonist （AZD1981） on eosinophil activity and symptoms in chronic spontaneous urticaria［J］. Int Arch Allergy Immunol, 2019,179（1）:21⁃30. doi: 10.1159/000496162.
［30］	Brightling CE, Gaga M, Inoue H, et al. Effectiveness of fevipiprant in reducing exacerbations in patients with severe asthma （LUSTER⁃1 and LUSTER⁃2）: two phase 3 randomised controlled trials［J］. Lancet Respir Med, 2021,9（1）:43⁃56. doi: 10.1016/S2213⁃2600（20）30412⁃4.
［31］	Lee JK, Simpson RS. Dupilumab as a novel therapy for difficult to treat chronic spontaneous urticaria［J］. J Allergy Clin Immunol Pract, 2019,7（5）:1659⁃1661.e1. doi: 10.1016/j.jaip. 2018.11.018.
［32］	Abadeh A, Lee JK. Long⁃term follow⁃up of patients treated with dupilumab for chronic spontaneous urticaria: a case report［J］. SAGE Open Med Case Rep, 2022,10:2050313X221117702. doi: 10.1177/2050313X221117702.
［33］	Maurer M, Casale TB, Saini SS, et al. Dupilumab in patients with chronic spontaneous urticaria （LIBERTY⁃CSU CUPID）: two randomized, double⁃blind, placebo⁃controlled, phase 3 trials［J］. J Allergy Clin Immunol, 2024,154（1）:184⁃194. doi: 10.1016/j.jaci.2024.01.028.
［34］	Bernstein JA, Singh U, Rao MB, et al. Benralizumab for chronic spontaneous urticaria［J］. N Engl J Med, 2020,383（14）:1389⁃1391. doi: 10.1056/NEJMc2016395.
［35］	Sabag DA, Matanes L, Bejar J, et al. Interleukin⁃17 is a potential player and treatment target in severe chronic spontaneous urticaria［J］. Clin Exp Allergy, 2020,50（7）:799⁃804. doi: 10. 1111/cea.13616.
［36］	Sofen H, Bissonnette R, Yosipovitch G, et al. Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor β antibody, in moderate⁃to⁃severe prurigo nodularis: a randomised, double⁃blind, placebo⁃controlled, phase 2a study［J］. EClinicalMedicine, 2023,57:101826. doi: 10.1016/j.eclinm.2023. 101826.
［37］	Menzies⁃Gow A, Corren J, Bourdin A, et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma［J］. N Engl J Med, 2021,384（19）:1800⁃1809. doi: 10.1056/NEJMoa 2034975.
［38］	Alvarado D, Maurer M, Gedrich R, et al. Anti⁃KIT monoclonal antibody CDX⁃0159 induces profound and durable mast cell suppression in a healthy volunteer study［J］. Allergy, 2022,77（8）:2393⁃2403. doi: 10.1111/all.15262.
［39］	Wedi B. Inhibition of KIT for chronic urticaria: a status update on drugs in early clinical development［J］. Expert Opin Investig Drugs, 2023,32（11）:1043⁃1054. doi: 10.1080/13543784.2023. 2277385.
［40］	Karra L, Berent⁃Maoz B, Ben⁃Zimra M, et al. Are we ready to downregulate mast cells?［J］. Curr Opin Immunol, 2009,21（6）:708⁃714. doi: 10.1016/j.coi.2009.09.010.
［41］	Altrichter S, Staubach P, Pasha M, et al. An open⁃label, proof⁃of⁃concept study of lirentelimab for antihistamine⁃resistant chronic spontaneous and inducible urticaria［J］. J Allergy Clin Immunol, 2022,149（5）:1683⁃1690.e7. doi: 10.1016/j.jaci.2021.12.772.
［42］	Metz M, Kolkhir P, Altrichter S, et al. Mast cell silencing: a novel therapeutic approach for urticaria and other mast cell⁃mediated diseases［J］. Allergy, 2024,79（1）:37⁃51. doi: 10.1111/all.15850.

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慢性自发性荨麻疹发病过程中肥大细胞作用及其靶向治疗进展

Role of mast cells in the pathogenesis of chronic spontaneous urticaria and advances in mast cell-targeted therapies

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