No Indication of Aberrant Neutrophil Extracellular Trap Release in Indolent or Advanced Systemic Mastocytosis

In disease states with chronic inflammation, there is a crosstalk between mast cells and neutrophil granulocytes in the inflamed microenvironment, which may be potentiated by tryptase. In systemic mastocytosis (SM), mast cells are constitutively active and tryptase is elevated in blood. Mast cell activation in SM leads to symptoms from various organs depending on where the active mast cells reside, for example, palpitations, flush, allergic symptoms including anaphylactic reactions, and osteoporosis. Whether neutrophil function is altered in SM is not well understood. In the current study, we assessed nucleosomal citrullinated histone H3 (H3Cit-DNA) as a proxy for neutrophil extracellular trap release in plasma from 55 patients with indolent and advanced SM. We observed a strong trend towards a correlation between leukocyte count, eosinophil count and neutrophil count and H3Cit-DNA levels in patients with advanced SM but not in indolent SM; however, no differences in H3Cit-DNA levels in SM patients compared with healthy controls. H3Cit-DNA levels did not correlate with SM disease burden, tryptase levels, history of anaphylaxis or presence of cutaneous mastocytosis; thus, there is no evidence of a general neutrophil extracellular trap release in SM. Interestingly, H3Cit-DNA levels and leukocyte counts were elevated in a subgroup of SM patients with aberrant mast cell CD2 expression, which warrants further investigation. In conclusion, we found no evidence of global increase in neutrophil extracellular trap release in SM. In patients with indolent and advanced systemic mastocytosis, we observed no increased neutrophil extracellular trap (NET) release compared with healthy controls. Furthermore, there was no difference in NET release between patients with indolent and advanced systemic mastocytosis.image