Interactions between eosinophils and IL-5Rα–positive mast cells in nonadvanced systemic mastocytosis - 18/09/24

Doi : 10.1016/j.jaci.2024.07.025

Guillaume Lefèvre, MD, PhD ^a,^b,^c,^⁎ , Jean-Baptiste Gibier, MD, PhD ^d, Antonino Bongiovanni, MSc ^e, Ludovic Lhermitte, MD, PhD ^f,^g,^h, Julien Rossignol, MD, PhD ^g,^h,ⁱ, Emilie Anglo, MSc ^a,^b, Arnaud Dendooven, MSc ^a,^b, Romain Dubois, MD ^d, Louis Terriou, MD ^a,^c,^j, David Launay, MD, PhD ^a,^c,^j, Stéphane Barete, MD, PhD ^k, Stéphane Esnault, PhD ^a,^b,^l, Laurent Frenzel, MD, PhD ^g,^h,ⁱ, Clément Gourguechon, MD ^m, Thomas Ballul, MD ^g,^h,ⁱ, Frédéric Dezoteux, MD, PhD ^a,^c,ⁿ, Delphine Staumont-Salle, MD, PhD ^a,^c,ⁿ, Marie-Christine Copin, MD, PhD ^o, Rachel Rignault-Bricard, MSc ^g, Thiago Trovati Maciel, PhD ^g, Gandhi Damaj, MD, PhD ^p, Meryem Tardivel, PhD ^e, Marie Crinquette-Verhasselt, MD ^d, Patrice Dubreuil, PhD ^q, Leila Maouche-Chrétien, PhD ^g, Julie Bruneau, MD, PhD ^g,^h,^r, Olivier Lortholary, MD, PhD ^g,^h, Nicolas Duployez, MD, PhD ^s, Hélène Behal, MD ^t, Thierry Jo Molina, MD, PhD ^g,^q, Olivier Hermine, MD, PhD ^g,^h,^i,^⁎
^a University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, and Institute for Translational Research in Inflammation (INFINITE), Lille, France
^b Institut d’Immunologie, CHU Lille, Lille, France
^c National Reference Center for Hypereosinophilic Syndromes (CEREO)
^d University of Lille, Institut de Pathologie, Centre de Biopathologie, CHU Lille, Lille, France
^e Centre National de la Recherche Scientifique (CNRS), INSERM, CHU Lille, University of Lille, Institut Pasteur de Lille, Lille, France
^f Laboratoire d’Onco-Hématologie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France
^g University of Paris, Institut Imagine, INSERM, Paris, France
^h French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker-Enfants Malades, AP-HP, Paris, France
ⁱ Department of Hematology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
^j Département de Médecine Interne et Immunologie Clinique, CHU Lille, Lille, France
^k CEREMAST, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Unit de Dermatologie, Sorbonne Université Paris, Paris, France
^l Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin–Madison School of Medicine and Public Health, Madison, Wis
^m Department of Hematology, CHU Amiens, Amiens, France
ⁿ Department of Dermatology, CHU Lille, Lille, France
^o Department of Pathology, CHU Angers, University of Angers, INSERM, CNRS, CRCI²NA, Angers, France
^p Institut d’Hématologie, University of Caen Normandie, Caen, France
^q Signaling, Hematopoiesis, and Mechanism of Oncogenesis (CRCM), CEREMAST, and Association Française pour les Initiatives de Recherche sur le Mastocyte et les Mastocytose (AFIRMM) studies, INSERM U1068; Institut Paoli-Calmettes; UM105, Aix-Marseille University; and CNRS, UMR7258, Marseille, France
^r Department of Pathology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
^s CNRS, INSERM, CHU Lille, Cancer Heterogeneity, Plasticity, and Resistance to Therapies (CANTHER), University of Lille, Institut d’Hématologie, CHU Lille, Lille, France
^t University of Lille, CHU Lille, Evaluation des Technologies de Santé et des Pratiques Médicales (METRICS), Lille, France

^∗Corresponding authors: Guillaume Lefèvre, MD, PhD, Institut d’Immunologie, CHU Lille, Bd Professeur Jules Leclercq, 59037 Lille Cedex, France.Institut d’ImmunologieCHU LilleBd Professeur Jules LeclercqLilleCedex59037France^∗Olivier Hermine, MD, PhD, Service d’Hématologie adulte, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris, France.Service d’Hématologie adulteHôpital Necker-Enfants Malades149 rue de SèvresParis75743France

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Wednesday 18 September 2024

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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Key words : Eosinophil, mast cell, systemic mastocytosis

Abbreviations used : Adv-SM, ASM, BM, BMM, EPX, HE, ISM, MC, MCL, MHC-II, NGS, Non–Adv-SM, ROI, SM, SM-AHN, SSM, WHO