Abstract
Mast cells (MCs) participate in diseases such as systemic mastocytosis (SM) and allergic conditions. Less well understood is the role of MCs in non-allergic inflammatory disorders like rheumatoid arthritis (RA). Studying definitive roles for MCs in human diseases has been hampered by the lack of a well-accepted biomarker for monitoring in vivo MC activation. This study aimed to investigate the utility of urinary tetranor PGDM (T-PGDM) as a biomarker of in vivo MC activation in patients with SM, and apply this biomarker to assess MC involvement in relation to RA disease activity. A prospective, cross-sectional cohort study was conducted to measure a major urinary metabolite of prostaglandin D2, T-PGDM. Urine samples were collected from patients with RA (n = 60), SM (n = 17) and healthy normal controls (n = 16) and T-PGDM excretion was determined by enzyme immunoassay as nanograms per milligram of urinary creatinine (ng/mg Cr). Mean urinary T-PGDM excretion was significantly higher (p < 0.01) in patients with SM compared to controls (37.2 vs. 11.5 ng/mg Cr) with 65% of SM patients showing elevated levels. One third of patients with RA had elevated T-PGDM excretion, and the mean level in the RA group (20.0 ng/mg Cr) was significantly higher than controls (p < 0.01). Medications inhibiting cyclooxygenase reduced T-PGDM excretion. Urinary T-PGDM excretion appears promising as a biomarker of in vivo MC activity and elevated levels in 33% of patients with RA provides evidence of MC activation in this disease.
Highlights
Mast cells (MCs) are granular, inflammatory cells with major roles in the immune and tissue repair systems [1]
This study has demonstrated that urinary 11,15-dioxo-9ahydrox-2,3,4,5-tetranor-prostan-1,20-dioic acid (T-PGDM) is a potentially useful biomarker of in vivo MC activity
We observed significantly higher mean urinary tetranor PGDM (T-PGDM) excretion in systemic mastocytosis (SM) patients compared to healthy controls, with elevated levels of T-PGDM excretion in a large proportion (65%) of the patients with SM
Summary
Mast cells (MCs) are granular, inflammatory cells with major roles in the immune and tissue repair systems [1]. Many beneficial immunological and physiological functions of MCs occur by their release of a range of mediators including histamine, the MC-specific serine proteases, tryptase and chymase, lipid-derived mediators including leukotrienes and prostaglandin D2 (PGD2), and a broad spectrum of cytokines [2, 3]. Measuring the quantity of mediators released from MCs provides a pathway to assessing MC activity in vivo. Measurements of metabolites including tryptase and histamine in both serum and urine are employed as diagnostic tools in mastocytosis syndromes [4]. These metabolites have been analysed in anaphylaxis and asthma. There has been interest in other MC metabolites including PGD2 as potential biomarkers for in vivo activity [7]. In vivo and in vitro, PGD2 is an unstable compound and is rapidly degraded into D-, F- and
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