title: Prostaglandin D2 metabolites as a biomarker of in vivo mast cell activation in systemic mastocytosis and rheumatoid arthritis.
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.
authors.affiliation: Faculty of Medicine University of New South Wales Sydney 2052 Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cho
authors.affiliation: Faculty of Medicine University of New South Wales Sydney 2052 Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Nguyen
authors.affiliation: Faculty of Medicine University of New South Wales Sydney 2052 Australia.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Bryant
authors.affiliation: Faculty of Medicine University of New South Wales Sydney 2052 Australia.
authors.forename: Sean G
authors.initials: SG
authors.lastname: O'Neill
authors.affiliation: Faculty of Medicine and Health Sciences Macquarie University Sydney 2109 Australia.
authors.forename: H Patrick
authors.initials: HP
authors.lastname: McNeil
keywords: Biomarker; mast cell; prostaglandin D metabolites; rheumatoid arthritis; systemic mastocytosis; tetranor PGDM