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Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We studied the distribution of TCD4<jats:sup>+<\/jats:sup> and TCD4<jats:sup>\u2212<\/jats:sup> cytotoxic cells and their subsets, as well as total NK\u2010 and B cells, in blood of 115 SM patients\u201438 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)\u2010 and 83 age\u2010matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage <jats:italic>KIT<\/jats:italic><jats:sup>D816V<\/jats:sup>, the alpha\u2010tryptasemia genotype (H\u03b1T) and the clinical manifestations of the disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SM patients showed decreased counts (vs. HD) of TCD4<jats:sup>\u2212<\/jats:sup> cytotoxic cells, NK cells and several functional subsets of TCD4<jats:sup>+<\/jats:sup> cells (total Th1, Th2\u2010effector memory, Th22\u2010terminal effector and Th1\u2010like Tregs), together with increased T\u2010follicular\u2010helper and Th1\/Th17\u2010like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC\u2010restricted <jats:italic>KIT<\/jats:italic><jats:sup>D816V<\/jats:sup> and in cases with a H\u03b1T<jats:sup>+<\/jats:sup> versus H\u03b1T<jats:sup>\u2212<\/jats:sup> genotype. Unique immune profiles were found among BMM and ISM patients with MC\u2010restricted <jats:italic>KIT<\/jats:italic><jats:sup>D816V<\/jats:sup> who displayed H\u03b1T, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results reveal altered T\u2010 and NK\u2010cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by <jats:italic>KIT<\/jats:italic><jats:sup>D816V<\/jats:sup>, the H\u03b1T genotype and specific clinical manifestations of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.16043","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T13:19:32Z","timestamp":1706793572000},"page":"1921-1937","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["T\u2010cell immune profile in blood of systemic 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