Proteomic and transcriptomic screening demonstrates increased mast cell–derived CCL23 in systemic mastocytosis
Journal of Allergy and Clinical Immunology, 2023
Söderlund S., Boey D., van Midden W., Kjellander M., Ax K., Qian H., Dahlin J., Ungerstedt J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Patient Stratification | Plasma |  Olink Target 96 |
Abstract
Background: 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.
Objective: Our aim was to identify mast cell-derived proteins that could potentially serve as blood biomarkers for indolent and advanced forms of systemic mastocytosis.
Methods: We performed a plasma proteomics screen coupled with single-cell transcriptomics analysis in systemic mastocytosis patients and healthy subjects.
Results: Plasma proteomics screening identified 19 proteins upregulated in indolent disease compared to healthy, and 16 proteins in advanced disease compared to indolent. Among these, five proteins, CCL19, CCL23, CXCL13, IL10 and IL12Rβ1, were higher in indolent relative to healthy and in advanced disease compared to indolent. Single-cell RNA sequencing demonstrated that CCL23, IL10 and IL6 were selectively produced by mast cells. Notably, plasma CCL23 levels correlated positively to known markers of systemic mastocytosis disease severity namely tryptase levels, percentage bone marrow mast cell infiltration, and to IL6.
Conclusion: 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, suggesting CCL23 as a specific systemic mastocytosis biomarker. In addition, the combination of CCL19, CCL23, CXCL13, IL10 and IL12Rβ1 may be useful for defining disease stage.