The following is a summary of “T-cell immune profile in blood of systemic mastocytosis: Association with disease features,” published in the February 2024 issue of Allergy & Immunology by Pérez-Pons, et al.
Systemic mastocytosis (SM) is a diverse disease marked by the expansion of KIT-mutated mast cells (MC) that exhibit activated characteristics and release mediators affecting the tumor microenvironment and immune cells. Despite the known role of MC mediators, there is a limited understanding of how these mediators influence lymphocyte subsets in SM. For a study, researchers sought to investigate the distribution of lymphocyte subsets in the blood of patients with various SM subtypes and to explore the associations between these subsets and other disease characteristics.
They analyzed the distribution of TCD4+ and TCD4– cytotoxic lymphocytes, including their subsets, as well as total NK and B cells in the blood of 115 SM patients, categorized into 38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), and 10 aggressive SM (ASM) cases, compared to 83 age-matched healthy donors (HD). They employed spectral flow cytometry and the EuroFlow Immunomonitoring panel to assess these lymphocyte populations. We also correlated these distributions with multilineage KITD816V mutation status, the alpha-tryptasemia genotype (HαT), and various clinical manifestations of the disease.
Compared to HD, patients with SM exhibited significantly decreased counts of TCD4– cytotoxic cells, NK cells, and several functional subsets of TCD4+ cells, including total Th1 cells, Th2-effector memory cells, Th22-terminal effector cells, and Th1-like Tregs. Conversely, there was an increase in T-follicular-helper cells and Th1/Th17-like Tregs. These immune profile alterations were associated with specific SM subtypes, the pattern of KITD816V involvement across lineages, and the presence or absence of the HαT genotype. Notably, BMM and ISM patients with MC-restricted KITD816V and HαT+ displayed unique immune profiles correlated with clinical features such as anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing, and gastrointestinal symptoms.
The study revealed distinct alterations in T- and NK-cell immune profiles in the blood of SM patients, which vary depending on the disease subtype, the pattern of KITD816V mutation involvement, the HαT genotype, and specific clinical manifestations. The findings offered insights into how SM-associated immune dysfunctions correlate with disease characteristics and may inform future therapeutic strategies.
Reference: onlinelibrary.wiley.com/doi/10.1111/all.16043
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