Massive release of TH2 cytokines induced a cytokine storm during a severe mast cell activation event in a patient with indolent systemic mastocytosis - 04/08/22
, Robin Ristl, PhD b, Jakob Mühlbacher, MD, PhD c, Peter Valent, MD d, Markus Wahrmann, PhD e, Bernd Jilma, MD aAbstract |
Background |
In subjects with systemic mastocytosis, the number of mast cells is elevated many fold. These patients frequently experience 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 a patient with indolent systemic mastocytosis were used for this study. A total of 41 chemokines and cytokines were simultaneously measured in triplicate and at multiple time points during 2 severe and 2 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 chemokine (C-C motif) ligand 3, IL-1ra, IL-5, IL-6, IL-10, IL-13, and granulocyte-macrophage colony-stimulating factor concentrations were statistically significantly elevated 29-, 99-, 44-, 280-, 93-, 7-, and 6-fold above baseline, respectively. A highly 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 INF-α, INF-γ, and TNF-α 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 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.
Il testo completo di questo articolo è disponibile in PDF.Key words : Mast cell activation, mastocytosis, TH2 cytokines, cytokine storm, cytokine release syndrome
Abbreviations used : BH_corr, BL, CCL, CXCL, GM-CSF, MC, MCA, MCAS, PDGF, SD, SIRS, VEGF
Mappa
| Supported by the Austrian Science Fund (grants F4704-B20 and P32470-B to P.V.). |
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| Disclosure of potential conflict of interest: T. Boehm and B. Jilma are coinventors of a patent regarding the use of recombinant human diamine oxidase in the treatment of conditions with excess histamine. P. Valent received consultancy honoraria from Novartis, Blueprint, Pfizer, and Celgene. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 150 - N° 2
P. 406 - Agosto 2022 Ritorno al numero
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