Prostaglandin D₂metabolites as a biomarker ofin vivomast 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.

Effect of human breast milk on biological metabolism in infants

“…Urinary t-PGDM is a potentially useful biomarker of in vivo activity of mast cells. 54 Furthermore, intestinal mucosal mast cells are critically involved in the development of food-induced allergic disorders. 55 A difference in LC-PUFA content between BM and formula might affect intestinal mucosal mast cells during infancy.…”

Lipidomic analysis of urinary exosomes from hereditary α‐tryptasemia patients and healthy volunteers

“…We thought high levels of prostaglandin D2 (PGD2) could be responsible for higher tubular exosome release, and a high level of PLD in HαT patients can be responsible for a greater production of exosomes from mast cells. It has been previously shown that PGD2 urine metabolites are increased in patients with mast cell disorders and these metabolites can be used as biomarkers . In addition, PGE2 activates mast cell responses by inducing the mTORC2 pathway .…”

“…It has been previously shown that PGD2 urine metabolites are increased in patients with mast cell disorders and these metabolites can be used as biomarkers. 47,48 In addition, PGE2 activates mast cell responses by inducing the mTORC2 pathway. 49 Prostaglandin E2 and Prostaglandin I2 are known to increase renal blood flow and glomerular filtration rate via vasodilation.…”

Regulation of inflammation by lipid mediators in oral diseases

“…While levels of total unmodified prostaglandin in urine have been correlated with only a few diseases (e.g., cardiovascular disease (Raatz et al , ) and anaphylaxis (Lieberman, )), levels of prostaglandin metabolites in urine have attracted more scrutiny. High levels of the PGD 2 metabolite tetranor PGDM in urine have been correlated with Duchenne muscular dystrophy, systemic mastocytosis, rheumatoid arthritis, colitis, and colon cancer (Nakagawa et al , ,b; Iwanaga et al , ; Cho et al , ). High levels of urinary PGE 2 metabolite levels appear to be associated with colorectal adenoma (Shrubsole et al , ; Davenport et al , ), pancreatic cancer (Zhao et al , ), and breast cancer in postmenopausal women (Cui et al , ).…”