A new sensitive panel for in vivo monitoring of mast cell activation in urine samples

Background: Mast cells are activated in asthma and mast cell activating syndromes (MAS) such as systemic mastocytosis and chronic urticaria. Serum tryptase is used clinically for diagnosis of MAS. The urinary excretion of the prostaglandin (PG) D 2 metabolite 11β-PGF 2 α is established as a sensitive marker of mast cell activation in trigger-factor evoked airway obstruction. More recently, another PGD 2 metabolite, tetranor-PGDM has been identified as the major metabolite in urine. Moreover, a new selective LC/MS method for measurement of the major urinary histamine metabolite 1-methyl-4-midazoleacetic acid ( t -MIAA) has been introduced (Kolmert et al Anal Bioanal Chem. 2014). We therefore compared baseline urinary excretion of metabolites of PGD 2 and histamine with measurement of serum (S)tryptase. Methods: Urine and blood collected from 9 healthy volunteers, 11 asthmatics (A), 6 subjects with chronic urticaria (CU),and 19 patients with mastocystosis (MC), all being stable at the time of collection. Analysis of 11β-PGF 2 α and tetranor-PGDM were made using both a routine enzyme immunoassay (EIA) and UPLC-MS/MS (Balgoma et al Anal Chem 2013), t -MIAA according to Kolmert et al, and serum-tryptase by EIA at the hospital laboratory. Results: The majority of patients with MC exhibited high levels of all urinary mediators as compared to healthy volunteers; 1.5-30 fold increases. In contrast, serum-tryptase was only increased in some patients diagnosed with MC and there was no significant alteration of the urinary metabolites among the asthmatic patients. Conclusion: The data support that baseline urinary excretion of lipid and histamine metabolites are sensitive non-invasive markers of mast cell activation.