Researchers reported that a significant release of Th2 cytokines induced a cytokine storm in a patient with indolent systemic mastocytosis (SM) when the patient experienced a severe mast cell activation event, as published in the Journal of Allergy and Clinical Immunology

Many patients with SM experience recurrent severe mast cell activation attacks, which can be life-threatening. However, we know little about the underlying mechanisms that trigger them. Scientists have proposed that excessive histamine release might contribute to the symptoms experienced by patients during protracted episodes of severe mast cell activation, but this is unlikely to be the sole factor driving the attacks.

The lack of research on the underlying mechanisms of severe mast cell activation events impedes the ability of medical researchers to propose new therapeutic agents. Current treatment regimes, such as antihistamines, glucocorticoids, fluid replacement, and symptomatic relief of fever or nausea, often do not lead to satisfactory results. 

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Boehm and colleagues decided to investigate the derangement of chemokine and cytokine concentrations during severe severe mast cell activation episodes. They collected blood samples from a 43-year-old male who was diagnosed with KIT D816V positive indolent systemic mastocytosis in 2008.

He experienced recurrent severe mast cell activation episodes once or twice each year, with the most severe mast cell activation event occurring in February 2018. Boehm and colleagues measured a total of 41 chemokines and cytokines simultaneously in triplicate and at various time points during 2 severe and 2 moderate-severe mast cell activation attacks.

The research team found that Th2 cytokines were dramatically increased during the acute phase of a severe severe mast cell activation event. In addition, histamine concentration showed high correlation coefficients with various parameters during the severe severe mast cell activation event, suggesting that they might have originated from activated mast cells.

“We provide strong evidence that severe, life-threatening [severe mast cell activation] events are orchestrated by the release of several potent proinflammatory chemokines and prototypical Th2 cytokines,” Boehm et al concluded.

Reference

Boehm T, Ristl R, Mühlbacher J, Valent P, Wahrmann M, Jilma B. Massive release of Th2 cytokines induced a cytokine storm during a severe mast cell activation event in an indolent systemic mastocytosis patientJ Allergy Clin Immunol. Published online April 30, 2022. doi:10.1016/j.jaci.2022.04.023