J Allergy Clin Immunol. 2022 Apr 30:S0091-6749(22)00617-0. doi: 10.1016/j.jaci.2022.04.023. Online ahead of print.
ABSTRACT
BACKGROUND: In subjects with systemic mastocytosis the number of mast cells is elevated manifold. These patients frequently suffer unpredictable and recurrent life-threatening mast cell activation (MCA) events.
OBJECTIVE: Our aim was to analyze the derangements of chemokine and cytokine concentrations during severe MCA attacks METHODS: Samples from an indolent systemic mastocytosis patient were used for this study. A total of 41 chemokines and cytokines were simultaneously measured in triplicate and at multiple time points during two severe and two moderate MCA events. These were compared to 3 to 5 baseline samples, taken when clinical symptoms were not present.
RESULTS: During the severe MCA event, which required 2 days of treatment in the intensive care unit, peak CCL3, IL-1ra, IL-5, IL-6, IL-10, IL-13 and GM-CSF concentrations were statistically significantly elevated 29-, 99-, 44-, 280-, 93-, 7- and 6-fold above baseline respectively. A very similar pattern was observed during the second severe MCA event. In the moderate MCA event with PCR-proven Influenza A infection, the Th1-associated cytokines INFα, INFγ and TNFα were only statistically significantly elevated 5- to 7-fold above baseline. The correlation coefficients between highly elevated histamine and cytokine concentrations during the acute phase were >95% indicating the same cellular origin, possibly activated mast cells.
CONCLUSIONS: One of the severe MCA events led to life-threatening symptoms over several days. During this event, the massive release of Th2 cytokines induced a hyperinflammatory state, fulfilling recently published criteria for cytokine release syndrome. Administration of IL-6 and IL-5 inhibiting biologicals might significantly shorten the acute phase of severe MCA events, likely offering significant clinical benefits to mastocytosis patients.
PMID:35504498 | DOI:10.1016/j.jaci.2022.04.023
