TY - JOUR
T1 - Altered leukocyte subsets and immune proteome indicate proinflammatory mechanisms in mastocytosis
AU - Hermans, Maud A.W.
AU - Heeringa, Jorn J.
AU - Swagemakers, Sigrid G.A.
AU - Schrijver, Benjamin
AU - van Daele, Paul L.A.
AU - van der Spek, Peter J.
AU - van Hagen, P. Martin
AU - van Zelm, Menno C.
AU - Dik, Wim A.
N1 - 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
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123683570&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2021.12.786
DO - 10.1016/j.jaci.2021.12.786
M3 - Article
C2 - 35026208
AN - SCOPUS:85123683570
SN - 0091-6749
VL - 150
SP - 146-156.e10
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -