Interactions Between Eosinophils and IL5Rα+ Mast Cells in Non-Advanced Systemic Mastocytosis.

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

Edité par CCSD ; Elsevier -

International audience. BackgroundBidirectional 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.ObjectiveTo describe blood and BM eosinophil characteristics in SM.MethodsA large collection of BM biopsies 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.ResultsEosinophil 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 non-advanced-SM (n=37 BM biopsies) compared to both controls (n=8, p=0.0003) and to advanced SM (n=24, p=0.014). In non-advanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r=0.38, p=0.038), eosinophils count in BM biopsies (r=0.45, p=0.007), EPX staining (r=0.37, p=0.035) and eosinophil degranulation (r=0.39, p=0.023). Eosinophil counts in BM biopsies also correlated with MC counts (r=0.47, p=0.006) and KIT staining surface (r=0.49, p=0.003). BM MCs expressed interleukin-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils display several increased surface markers compared to controls, suggesting an activated state.ConclusionOur data suggest a possible crosstalk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in non-advanced-SM not fully controlled by other therapies.

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