Abstract
BackgroundUncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis.ObjectiveThis study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA+), CMCD patients without anaphylaxis (CMCD/ANA-), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA+) and patients with a non-mast cell haematological pathology (NMHP).MethodsThis study included 20 patients with CMCD/WVA+, 24 with CMCD/ANA-, 19 with WVA+, 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included.ResultsHigher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations.ConclusionPatients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis.
Highlights
Clonal mast cell disorders (CMCD) originate from morphological and immunophenotypical aberrant mast cells (MCs) that proliferate abnormally and accumulate in different organs [1]
In the patients with wasp venom anaphylaxis, there was no significant difference between specific IgE (sIgE) and the sIgE-to-total IgE (tIgE) ratios (Supplementary Figure 3)
Despite significant progress in our understanding of the molecular mechanism behind anaphylaxis, it remains difficult to predict the risk for anaphylaxis in patients with or without a CMCD
Summary
Clonal mast cell disorders (CMCD) originate from morphological and immunophenotypical aberrant mast cells (MCs) that proliferate abnormally and accumulate in different organs [1]. In most cases, this abnormal proliferation is driven by a somatic gainof-function mutations of the KIT receptor, known as CD117. Patients with CMCD have a higher MC burden and a bST of >20 ng/mL is a minor criterion for the diagnosis [7]. A study by van Anrooij et al, showed that the prevalence of Hymenoptera venom anaphylaxis in patients with systemic mastocytosis (SM) increased up until the 6th decile of bST (28 ng/mL) but decreased with higher levels of bST [9]. Uncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis
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