Prostaglandin DM (PGDM)

Immunology

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Description

Prostaglandins are a group of lipid, hormone-like substances derived from arachidonic acid [1]. They participate in a wide range of functions such as the contraction and relaxation of smooth muscle, the dilation and constriction of blood vessels, control of blood pressure, and modulation of inflammation [1]. Prostaglandins are one of several substances (along with histamine and tryptase) which are present in the preformed granules within mast cells [1,2]. When mast cells are activated by antigen cross-linking IgE on the cell surface they degranulate and the contents are released into the circulation [1,2]. Prostaglandin D2 (PGD2) is a strong bronchoconstrictor which plays a pharmacological role in allergic and asthmatic anaphylaxis, and in mast cell disease (e.g. systemic mastocytosis) [2,3]. It is synthesised predominantly in mast cells by the enzyme glutathione-dependent PGD synthase. PGD2 is unstable and therefore has a short half-life (1-30 minutes). It is readily broken down into various metabolites, a major metabolite being 11beta-PGF2alpha [1,4]. This metabolite shows greater stability over its precursor [1]. PGD2 is unstable and is readily broken down into various metabolites, major urinary metabolites being 11beta-PGF2alpha and tetranor-prostaglandin DM (PGDM) [1,4,5]. The concentration of PGDM is reflective of the concentration of its precursor PGD2 therefore the measurement of urine PGDM of may be useful in investigations into allergic and asthmatic anaphylaxis, and mast cell disease (e.g. systemic mastocytosis) [4,6]. It is recommended that prostaglandin levels are measured on a 24 hour urine sample when investigating mast cell activation syndrome (MCAS) as symptom flares and the short half-life of mast cell mediators can lead to a normal result in spot urine samples [7,8]. Some patients with MCAS may not have raised mast cell mediator levels (tryptase, urine methylhistamine and prostaglandins) unless they are symptomatic. If there is good clinical history but negative results, it is recommended that the tests are repeated on a spot urine sample when the patient is symptomatic [7,8].

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Indications

Investigation of Mast Cell Activation Syndrome (MCAS) and anaphylaxis.

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Sample Type

5mL urine, no preservative. 24 hour collection advised if investigation MCAS. Spontaneous urine sample following allergic reaction followed by a baseline sample taken 24 hours post reaction if investigating anaphylaxis. Requests from outside Sheffield: Freeze sample prior to dispatch and transport frozen sample at ambient temperature via Royal Mail or Courier (dry ice not required).

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Reference Range

Normal range <2300ng/mmol creatinine.

Normal range verified in-house.

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Turnaround Time

Within 4 weeks

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Testing Frequency

3 weeks

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References

Ricciotti E. FitzGerald GA. Prostaglandins and Inflammation. Arterioscler Thromb Vasc Biol. 2011; 31(5): 986-1000. [Ref 1].
Frieri M, Patel R and Celestin J. Mast Cell Activation Syndrome: A Review. Curr Allergy Asthma Rep. 2013; 13: 27-32. [Ref 2].
Molderings GJ, Brettner S, Homann J, et al. Mast cell activation disease: a concise practical guide for diagnostic workup and therapeutic options. Journal of Haematology & Oncology. 2011; 4: 1-10. [Ref 3].
Ono E, et al. Increased production of cysteinyl leukotrienes and prostaglandin D2 during human anaphylaxis. Clinical and Experimental Allergy 2008:39; 72-80. [Ref 4].
Song, WL et al. Tetranor PGDM, an Abundant Urinary Metabolite Reflects Biosynthesis of Prostaglandin D2 in Mice and Humans. The Journal of Biological Chemistry 2008:283(2); 1179-1188. [Ref 5].
Higashi,N et al. Urinary tetranor-PGDM concentrations in aspirin-intolerant asthma and anaphylaxis. Journal of Allergy and Clinical Immunology. 2011: 129 (2); 557-559.e2 [Ref 6].
Afrin LB. Presentation, diagnosis and management of mast cell activation syndrome. Mast cells. 2013. Chapter 6, pp 155-231. [Ref 7]
Akin C, Valent P and Metcalf D. Mast cell activation syndrome: Proposed diagnostic criteria: Towards a global classification for mast cell disorders. J Allergy Clin Immunol. 2010. 126(6): 1099-1111. [Ref 8].

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See Also

Prostaglandin D2
Prostaglandin F2 Alpha
Urine Methylhistamine
Tryptase

Please note: the above information is subject to change and we endeavour to keep this website up to date wherever necessary.