Interactions between eosinophils and IL-5Rα-positive mast cells in nonadvanced systemic mastocytosis.

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology Pub Date : 2024-12-01 Epub Date: 2024-08-14 DOI:10.1016/j.jaci.2024.07.025

Guillaume Lefèvre, Jean-Baptiste Gibier, Antonino Bongiovanni, Ludovic Lhermitte, Julien Rossignol, Emilie Anglo, Arnaud Dendooven, Romain Dubois, Louis Terriou, David Launay, Stéphane Barete, Stéphane Esnault, Laurent Frenzel, Clément Gourguechon, Thomas Ballul, Frédéric Dezoteux, Delphine Staumont-Salle, Marie-Christine Copin, Rachel Rignault-Bricard, Thiago Trovati Maciel, Gandhi Damaj, Meryem Tardivel, Marie Crinquette-Verhasselt, Patrice Dubreuil, Leila Maouche-Chrétien, Julie Bruneau, Olivier Lortholary, Nicolas Duployez, Hélène Behal, Thierry Jo Molina, Olivier Hermine

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引用次数: 0

Abstract

Background: Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown.

Objective: We described blood and BM eosinophil characteristics in SM.

Methods: A large collection of BM biopsy samples was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence.

Results: Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in nonadvanced SM (n = 37 BM biopsy samples) compared with both controls (n = 8, P = .0003) and advanced SM (n = 24, P = .014). In nonadvanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r = 0.38, P = .038), eosinophils count in BM biopsy samples (r = 0.45, P = .007), EPX staining (r = 0.37, P = .035), and eosinophil degranulation (r = 0.39, P = .023). Eosinophil counts in BM biopsy samples also correlated with MC counts (r = 0.47, P = .006) and KIT staining surface (r = 0.49, P = .003). BM MCs expressed IL-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils displayed several increased surface markers compared with controls, suggesting an activated state.

Conclusion: Our data suggest possible cross talk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in nonadvanced SM not fully controlled by other therapies.

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非晚期系统性肥大细胞增多症中嗜酸性粒细胞与 IL5Rα+ 肥大细胞之间的相互作用

背景：据报道，在各种过敏性疾病中，嗜酸性粒细胞和肥大细胞（MC）之间存在双向相互作用。骨髓（BM）嗜酸性粒细胞增多在全身性肥大细胞增多症（SM）中很常见，其次是血液嗜酸性粒细胞增多，但其意义尚不清楚：描述系统性肥大细胞增多症患者血液和骨髓嗜酸性粒细胞的特征：方法：使用免疫组化染色和全切片成像技术分析了大量的骨髓活组织切片。嗜酸性粒细胞过氧化物酶（EPX）染色检测嗜酸性粒细胞和细胞外颗粒，KIT染色检测MCs。使用流式细胞术和免疫荧光进行了补充分析：结果：在SM的BM MC浸润内或周围观察到嗜酸性粒细胞浸润和大面积嗜酸性粒细胞脱颗粒。与对照组（8 例，P=0.0003）和晚期 SM（24 例，P=0.014）相比，非晚期 SM（37 例 BM 活检样本）的 EPX 染色表面更高，突出显示完整的嗜酸性粒细胞和嗜酸性粒细胞脱颗粒。在非晚期 SM 中，血清胰蛋白酶水平与生化组织抽吸物中嗜酸性粒细胞计数百分比（斯皮尔曼 r 系数 r=0.38，p=0.038）、生化组织活检中嗜酸性粒细胞计数（r=0.45，p=0.007）、EPX 染色（r=0.37，p=0.035）和嗜酸性粒细胞脱颗粒（r=0.39，p=0.023）之间呈正相关。BM 活检中的嗜酸性粒细胞数量也与 MC 数量（r=0.47，p=0.006）和 KIT 染色表面（r=0.49，p=0.003）相关。BM MCs表达白细胞介素-5受体和其他常见的嗜酸性粒细胞细胞因子/趋化因子受体，与对照组相比，血液中的嗜酸性粒细胞显示出几种增加的表面标记物，这表明嗜酸性粒细胞处于活化状态：我们的数据表明 MCs 和嗜酸性粒细胞之间可能存在串扰，支持 MCs 释放胰蛋白酶和 MCs 活化相关症状。这为其他疗法无法完全控制的非晚期SM患者靶向治疗嗜酸性粒细胞提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

期刊介绍： The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.