Altered leukocyte subsets and immune proteome indicate proinflammatory mechanisms in mastocytosis
Journal of Allergy and Clinical Immunology, 2022
Hermans M., Heeringa J., Swagemakers S., Schrijver B., van Daele P., van der Spek P., van Hagen P., van Zelm M., Dik W.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology Patient Stratification | Serum |  Olink Target 96 |
Abstract
Background: Indolent systemic mastocytosis (ISM) is characterized by pathological 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: To investigate peripheral leukocyte compartments and serum immune proteome in ISM.
Methods: Peripheral blood leukocyte phenotyping using flowcytometry 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 (pDC) and monocytes were significantly decreased while T-helper 2 cells were increased in peripheral blood of ISM patients. Furthermore, a shift from naïve to memory T-cells was observed. Hierarchical clustering of the serum proteome revealed two distinct subgroups within ISM patients. In subgroup A (n=8), 62 proteins were significantly overexpressed, whereas subgroup B (n=12) was comparable to healthy controls. Patients in subgroup A displayed upregulated signaling pathways downstream of Toll-like receptor 4, TNF-α and interferon-γFatigue was more often present in subgroup A compared to B (75% vs. 33% respectively, p 0.06).
Conclusions: Altered distribution of leukocyte subsets and a pro-inflammatory proteome were observed in subsequent two cohorts of ISM patients. We hypothesize that neoplastic mast cells recruit and activate pDC, monocytes and T-cells leading to a vicious cycle of inflammation.