Department of Medicine and Cytometry Service (NUCLEUS), Cancer Research Center (IBMCC, USAL-CSIC), Universidad de Salamanca, Salamanca, Spain.
Biomedical Research Networking Center Consortium (CIBERONC; CB16/12/00400), Madrid, Spain.
Allergy. 2024 Jul;79(7):1921-1937. doi: 10.1111/all.16043. Epub 2024 Feb 1.
Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. 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.
We studied the distribution of TCD4 and TCD4 cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KIT, the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease.
SM patients showed decreased counts (vs. HD) of TCD4 cytotoxic cells, NK cells and several functional subsets of TCD4 cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KIT and in cases with a HαT versus HαT genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KIT who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms.
Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KIT, the HαT genotype and specific clinical manifestations of the disease.
系统性肥大细胞增多症（SM）是一种异质性疾病，其特征为 KIT 突变的肥大细胞（MC）扩增。KIT 突变的 MC 表现出激活的特征，并释放可能作用于肿瘤微环境和其他免疫细胞的 MC 介质。在此，我们研究了不同 SM 亚型患者血液中淋巴细胞亚群的分布，并确定了其与其他疾病特征的关系。
我们使用光谱流式细胞术和 EuroFlow 免疫监测面板研究了 115 名 SM 患者（38 名骨髓肥大细胞增多症 [BMM]、67 名惰性 SM [ISM]、10 名侵袭性 SM [ASM]）和 83 名年龄匹配的健康供体（HD）血液中 TCD4 和 TCD4 细胞毒性细胞及其亚群以及总 NK 和 B 细胞的分布，并将其与多谱系 KIT、α-色氨酸血症基因型（HαT）和疾病的临床表现相关联。
SM 患者的 TCD4 细胞毒性细胞、NK 细胞和 TCD4 细胞的几个功能亚群（总 Th1、Th2 效应记忆、Th22 终末效应和 Th1 样 Tregs）计数降低（与 HD 相比），同时 T 滤泡辅助细胞和 Th1/Th17 样 Treg 计数增加，与 SM 的不同诊断亚型的不同免疫特征相关，与多谱系 KIT 和 MC 受限 KIT 中的病例相关与 HαT 基因型相比，MC 受限 KIT 的 HαT、过敏反应、蜂毒液过敏、骨病、瘙痒、潮红和 GI 症状的 ISM 和 BMM 患者存在独特的免疫特征。
我们的研究结果揭示了 SM 血液中 T 和 NK 细胞免疫特征的改变，这些改变因疾病亚型、KIT 参与造血的模式、HαT 基因型和疾病的特定临床表现而异。
