The number of mast cells in various organs is manifold elevated in individuals with systemic mastocytosis. Degranulation can lead to life-threatening symptomatology. No data have been published about the alterations of the metabolome and lipidome during an attack.
To analyze metabolomics and lipidomics changes during the acute phase of a severe mast cell activation event.
Forty-three metabolites and 11 lipid classes comprising 200 subvariants from multiple plasma samples in duplicate, covering 72 hours of a severe mast cell activation attack with nausea and vomiting, were compared to two baseline samples using quantitative liquid chromatography mass spectrometry.
A strong enterocyte dysfunction reflected in an almost 20-fold reduction in the functional small bowel length extrapolated from strongly reduced ornithine and citrulline concentrations was very likely secondary to severe endothelial cell dysfunction with hypoperfusion and extensive vascular leakage. Highly increased histamine and lactate concentrations accompanied the peak in clinical symptoms. Elevated asymmetric and symmetric dimethylarginine combined with reduced arginine levels compromised endothelial nitric oxide synthase activity and nitric oxide signaling. Specific and extensive depletion of many lysophosphatidylcholine variants indicates localized autotaxin activation and lysophosphatidic acid release. A strong correlation of clinical parameters with histamine concentrations and symptom reduction after 100-fold elevated plasma diamine oxidase concentrations imply histamine is the key driver of the acute phase.
Rapid elimination of elevated histamine concentrations using recombinant human diamine oxidase, supplementation of lysophosphatidylcholine for immunomodulation, inhibition of autotaxin activity and/or blockade of lysophosphatidic acid receptors might represent new treatment options for life-threatening mast cell activation events.

Copyright © 2021. Published by Elsevier Inc.