Systemic mastocytosis is a heterogeneous group of mast cell-driven diseases, diagnosed by bone marrow sampling. However, there is a limited number of available blood disease biomarkers for non-invasive diagnosis and management of these patients. The aim of this study was to identify mast cell-derived proteins that might serve as blood biomarkers for indolent and advanced forms of systemic mastocytosis. The approach taken to achieve this was to combine plasma proteomics using the Olink® Target 96 Immuno-oncology panel with single cell RNAseq.
The analysis identified 19 proteins upregulated in indolent disease compared to healthy controls, and 16 proteins differentially regulated in advanced disease compared to indolent, and among these, CCL19, CCL23, CXCL13, IL10 and IL12Rβ1 functioned for both types of comparison. Single-cell RNAseq was then used to relate these findings to the disease source, showing that CCL23, IL10 and IL6 were selectively produced by mast cells.
Further investigations of plasma protein levels of CCL23 by (confirmed by ELISA) showed associations with known biological features of systemic mastocytosis (including tryptase levels and percentage bone marrow mast cell infiltration. The conclusion was that CCL23 is a specific, systemic biomarker for mastocytosis and that a combination of CCL19, CCL23, CXCL13, IL10 and IL12Rβ1 may be useful for defining different disease stages.
Söderlund S, Boey D, van Midden W, et al. A proteomic and transcriptomic screening demonstrate increased mast cell-derived CCL23 in systemic mastocytosis. (2023) Journal of Allergy & Clinical Immunology, DOI: 10.1016/j.jaci.2023.01.033
CCL23 is produced predominantly by mast cells in systemic mastocytosis and CCL23 plasma levels are associated with disease severity, correlating positively with established markers of disease burden
Söderlund et al. (2023)
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