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

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 systemic mastocytosis patients were furthermore stained to confirm expression. Results Serum levels of TIM-3 and GAL-9 were increased in systemic mastocytosis, particularly in advanced subtypes, compared to healthy controls. TIM-3 and GAL-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 GAL-9 in mastocytosis infiltrates in bone marrow. Conclusions Together, our results demonstrate for the first time that serum levels of TIM-3 and GAL-9 are increased in advanced systemic mastocytosis. Moreover, TIM-3 and GAL-9 are expressed in bone marrow infiltrates in mastocytosis. These findings provide a rationale for exploring TIM-3 and GAL-9 as diagnostic markers and eventually also therapeutic targets in systemic mastocytosis, particularly in advanced forms.