Massive release of TH2 cytokines induced a cytokine storm during a severe mast cell activation event in a patient with indolent systemic mastocytosis

Boehm, Thomas; Ristl, Robin; Mühlbacher, Jakob; Valent, Peter; Wahrmann, Markus; Jilma, Bernd

doi:10.1016/j.jaci.2022.04.023

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…Among BMM, elevated blood counts of Th2 CM further contributed to identify patients who had HVA. In line with these observations, dysregulation of the Th2 immune response has been previously reported as a potential causal mechanism for anaphylaxis 53,54 and MCA‐episodes where massive release of Th2 cytokines is observed 55 . These findings, together with the greater IgE plasma levels observed here among patients who had HVA as well as anaphylaxis, would further support the existence of an underlying dysregulated Th2 immune response in these two groups of patients.…”

Section: Discussionsupporting

confidence: 90%

“…In line with these observations, dysregulation of the Th2 immune response has been previously reported as a potential causal mechanism for anaphylaxis 53,54 and MCA-episodes where massive release of Th2 cytokines is observed. 55 These findings, together with the greater IgE plasma levels observed here among patients who had HVA as well as anaphylaxis, would further support the existence of an underlying dysregulated Th2 immune response in these two groups of patients. Interestingly, our results also revealed an association between increased Th2 CM TCD4 + cell counts in BMM and ISM patients with MC-restricted KIT D816V and a history of prior H.…”

Section: Discussionsupporting

confidence: 73%

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T‐cell immune profile in blood of systemic mastocytosis: Association with disease features

Pérez‐Pons,

Teodosio,

Jara‐Acevedo

et al. 2024

Allergy

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BackgroundSystemic 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.MethodsWe 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 KITD816V, the alpha‐tryptasemia genotype (HαT) and the clinical manifestations of the disease.ResultsSM 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 KITD816V and in cases with a HαT+ versus HαT− genotype. Unique immune profiles were found among BMM and ISM patients with MC‐restricted KITD816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms.ConclusionOur 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 KITD816V, the HαT genotype and specific clinical manifestations of the disease.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 73%

T‐cell immune profile in blood of systemic mastocytosis: Association with disease features

Pérez‐Pons,

Teodosio,

Jara‐Acevedo

et al. 2024

Allergy

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“…However, other studies have shown that mast cell activation can exert anti-tumor effects by stimulating the activity of cytotoxic T cells and natural killer cells, which recognize and attack cancer cells ( 52 ). In addition, mast cell activation can stimulate the production of cytokines and chemokines that recruit other immune cells, such as dendritic cells and macrophages, into the tumor microenvironment, thereby enhancing antitumor immunity reaction ( 53 ).…”

Section: Resultsmentioning

confidence: 99%

Immune function of colon cancer associated miRNA and target genes

et al. 2023

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IntroductionColon cancer is a complex disease that involves intricate interactions between cancer cells and theimmune microenvironment. MicroRNAs (miRNAs) have recently emerged as critical regulators of gene expression in cancer, including colon cancer. There is increasing evidence suggesting that miRNA dysregulation plays a crucial role in modulating the immune microenvironment of intestinal cancer. In particular, miRNAs regulate immune cell activation, differentiation, and function, as well as cytokine and chemokine production in intestinal cancer. It is urgent to fully investigate the potential role of intestinal cancer-related miRNAs in shaping the immune microenvironment.MethodsTherefore, this paper aims to identify miRNAs that are potentially associated with colon cancer and regulate a large number of genes related to immune function. We explored the role of these genes in colon cancer patient prognosis, immune infiltration, and tumor purity based on data of 174 colon cancer patients though convolutional neural network, survival analysis and multiple analysis tools.ResultsOur findings suggest that miRNA regulated genes play important roles in CD4 memory resting cells, macrophages.M2, and Mast cell activated cells, and they are concentrated in the cytokinecytokine receptor interaction pathway.DiscussionOur study enhances our understanding of the underlying mechanisms of intestinal cancer and provides new insights into the development of effective therapies. Additionally, identification of miRNA biomarkers could aid in diagnosis and prognosis, as well as guide personalized treatment strategies for patients with intestinal cancer.

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Notch2-dependent GATA3+ Treg cells alleviate allergic rhinitis by suppressing the Th2 cell response

Jiao

Xu²,

Qiao³

et al. 2022

International Immunopharmacology

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Massive release of TH2 cytokines induced a cytokine storm during a severe mast cell activation event in a patient with indolent systemic mastocytosis

Cited by 6 publications

References 45 publications

T‐cell immune profile in blood of systemic mastocytosis: Association with disease features

T‐cell immune profile in blood of systemic mastocytosis: Association with disease features

Immune function of colon cancer associated miRNA and target genes

Notch2-dependent GATA3+ Treg cells alleviate allergic rhinitis by suppressing the Th2 cell response

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