Altered leukocyte subsets and immune proteome indicate proinflammatory mechanisms in mastocytosis

Maud A.W. Hermans*, Jorn J. Heeringa, Sigrid G.A. Swagemakers, Benjamin Schrijver, Paul L.A. van Daele, Peter J. van der Spek, P. Martin van Hagen, Menno C. van Zelm, Wim A. Dik

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)
21 Downloads (Pure)


Background: Indolent systemic mastocytosis (ISM) is characterized by pathologic accumulation of mast cells. The mechanism behind its phenotypic heterogeneity is not well understood. Interaction of mast cells with other immune cells might cause systemic inflammation and thereby associated symptoms. Objective: We investigated peripheral leukocyte compartments and serum immune proteome in ISM. Methods: Peripheral blood leukocyte phenotyping using flow cytometry in a cohort of 18 adults with ISM and 12 healthy controls. Targeted proteomics was performed to measure 169 proteins associated with inflammation on serum of another 20 ISM patients and 20 healthy controls. Results: Proportions of plasmacytoid dendritic cells and monocytes were significantly decreased while TH2 cells were increased in peripheral blood of ISM patients. Furthermore, a shift from naive to memory T cells was observed. Hierarchical clustering of the serum proteome revealed 2 distinct subgroups within ISM patients. In subgroup A (n = 8), 62 proteins were significantly overexpressed, whereas those of subgroup B (n = 12) were comparable to healthy controls. Patients in subgroup A displayed upregulated signaling pathways downstream of Toll-like receptor 4, TNF-α, and IFN-γ. Fatigue was more often present in subgroup A compared to B (75% vs 33% respectively, P = .06). Conclusions: Altered distribution of leukocyte subsets and a proinflammatory proteome were observed in subsequent 2 cohorts of ISM patients. We hypothesize that neoplastic mast cells recruit and activate plasmacytoid dendritic cells, monocytes, and T cells, leading to a vicious cycle of inflammation.

Original languageEnglish
Pages (from-to)146-156.e10
JournalJournal of Allergy and Clinical Immunology
Issue number1
Publication statusPublished - 1 Jul 2022

Bibliographical note

Funding Information:
M.C.Z. is supported by an National Health and Medical Research Council (NHMRC) Senior Research Fellowship (GNT1117687) and an NHMRC Ideas grant (GNT2000773).

Publisher Copyright: © 2022 The Authors


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