CCL23 (chemokine ligand 23) has been suggested as a biomarker for systemic mastocytosis (SM), with CCL23 plasma cells associated with disease severity, according to findings from a study published in The Journal of Allergy and Clinical Immunology.

SM has been described as a heterogeneous group of disorders in which accumulation of neoplastic mast cells in bone marrow, skin, and other organs is detected. Subtypes of the disease range from indolent SM, in which symptoms of mast cell activation are reported but a normal life expectancy is anticipated, to advanced SM, in which bone marrow failure, organ impairment, and a dismal prognosis are predicted.

Because patients with SM present with heterogeneous symptoms, based on the organs affected, the diagnosis of SM is challenging. A limited number of blood disease biomarkers are available to assist in accurate disease diagnosis. The researchers of the current analysis sought to identify mast cell-derived proteins that might serve as blood biomarkers for indolent and advanced SM.

Patients who had been diagnosed with SM at the Center of Excellence for SM at Karolinska University in Stockholm, Sweden, according to criteria from the World Health Organization (WHO), were included in the study. The investigators performed a plasma proteomics screen, along with a single-cell transcriptomics analysis, in patients with SM and healthy controls.

A total of 39 participants with indolent SM, 9 with advanced SM, and 20 healthy controls were enrolled in the study. Further, 3 individuals who experienced unexplained anaphylaxis and elevated baseline serum tryptase levels, as well as 3 patients with cutaneous mastocytosis who underwent bone marrow sampling but did not meet the WHO criteria for SM, were evaluated for CCL23 plasma levels. Additionally, 8 individuals with chronic myeloid malignancy and no suspicion of SM, 6 patients with chronic myelomonocytic leukemia, and 2 individuals with myeloproliferative neoplasm were analyzed for CCL23 plasma levels as well.

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The plasma proteomics screen demonstrated that 19 proteins were higher among individuals with indolent SM than in healthy controls, 16 proteins were higher among those with advanced SM compared with those with indolent SM, and 25 proteins were higher among those with advanced SM than healthy controls. Of these proteins, 5 were higher in participants with indolent SM vs healthy controls, as well as in those with advanced SM vs indolent SM—that is, CCL19, CCL23, CXCL13, interleukin (IL)10, and IL12Rβ1.

Based on single-cell RNA sequencing, CCL23, IL10, and IL6 were produced selectively by mast cells. Plasma CCL23 levels correlated positively with known markers of SM disease severity, including tryptase levels, the proportion of bone marrow mast cell infiltration, and IL16.

“Based on these findings, we propose CCL23 as a biologically relevant potential biomarker for SM,” the authors indicated. “However, validation in an independent cohort is needed,” they concluded.


Söderlung S, Boey D, van Midden W, et al. A proteomic and transcriptomic screening demonstrate increased mast cell-derived CCL23 in systemic mastocytosis. J Allergy Clin Immunol. Published online February 23, 2023. doi:10.1016/j.jaci.2023.01.033