Increased TIM-3 and galectin-9 serum levels in patients with advanced systemic mastocytosis

Martina Konantz; Margaret Williams; Tamara Merkel; Antonia Reiss; Stefan Dirnhofer; Sara C Meyer; Peter Valent; Tracy I George; Alexandar Tzankov; Karin Hartmann

doi:10.1016/j.jaci.2023.07.001

Increased TIM-3 and galectin-9 serum levels in patients with advanced systemic mastocytosis

J Allergy Clin Immunol. 2023 Oct;152(4):1019-1024. doi: 10.1016/j.jaci.2023.07.001. Epub 2023 Jul 8.

Authors

Affiliations

¹ Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
² ARUP Laboratories, Salt Lake City, Utah; University of Utah, Salt Lake City, Utah.
³ Division of Allergy, Department of Dermatology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁴ Department of Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland; Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁶ Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, Vienna, Austria.
⁷ Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland; Division of Allergy, Department of Dermatology, University Hospital Basel and University of Basel, Basel, Switzerland. Electronic address: karin.hartmann@usb.ch.

PMID: 37423405
DOI: 10.1016/j.jaci.2023.07.001

Abstract

Background: Systemic mastocytosis is characterized by expansion of clonal mast cells in various tissues. Several biomarkers with diagnostic and therapeutic potential have recently been characterized in mastocytosis, such as the serum marker tryptase and the immune checkpoint molecule PD-L1.

Objective: We aimed to investigate whether serum levels of other checkpoint molecules are altered in systemic mastocytosis and whether these proteins are expressed in mastocytosis infiltrates in the bone marrow.

Methods: Levels of different checkpoint molecules were analyzed in serum of patients with different categories of systemic mastocytosis and healthy controls and correlated to disease severity. Bone marrow biopsies from patients with systemic mastocytosis were stained to confirm expression.

Results: Serum levels of TIM-3 and galectin-9 were increased in systemic mastocytosis, particularly in advanced subtypes, compared with healthy controls. TIM-3 and galectin-9 levels were also found to correlate with other biomarkers of systemic mastocytosis, such as serum tryptase and KIT D816V variant allele frequency in the peripheral blood. Moreover, we observed expression of TIM-3 and galectin-9 in mastocytosis infiltrates in bone marrow.

Conclusions: Together, our results demonstrate for the first time that serum levels of TIM-3 and galectin-9 are increased in advanced systemic mastocytosis. Moreover, TIM-3 and galectin-9 are expressed in bone marrow infiltrates in mastocytosis. These findings provide a rationale for exploring TIM-3 and galectin-9 as diagnostic markers and eventually therapeutic targets in systemic mastocytosis, particularly in advanced forms.

Keywords: Biomarker; KIT mutation; TIM-3; checkpoint receptor; galectin-9; mast cell; mastocytosis; tryptase.