Leukotriene E4, Urine

Although a random urine is acceptable, the preferred specimen is a 24 hour collection.

LAB00159

LAB00159
Mayo TC: RLT4 - Random Urine / TLTE4 - 24 Hour Urine

Leukotrine E4
Creatinine

5 mL of a Random or 24 Hour Urine Collection - For a 24 Hour urine, record the total volume and duration of collection.

3 mL of a Random or 24 Hour Urine Collection

Refrigerated

Refrigerated: 7 days

2-9 days

Leukotriene E4:
< or = 104 pg/mg Creatinine

Leukotrienes (LT) are eicosanoids generated from arachidonic acid via the 5-lipoxygenase pathway. Leukotriene E4 (LTE4) is the stable end product of this pathway and, therefore, regarded as a biomarker of total cysteinyl leukotriene production. Assessment of LTE4 in urine allows for noninvasive specimen collection and avoids artifactual formation of LT during phlebotomy. Generation of LTE4 occurs nonspecifically from active mast cells (MC), basophils, eosinophils, and macrophages, and modulated through a variety of mechanisms. Elevated concentrations of LTE4 are associated with both clonal (primary) and nonclonal (secondary and idiopathic) MC activation syndromes (MCAS). MCAS have been defined as a group of disorders in which patients experience symptoms precipitated by MC proinflammatory and vasoactive mediator release. Some of thse MC mediators contribute to physiologic processes and maintenance of tissue hemeostasis. 
 
Primary MCAS have clonal markers, such as the KIT Asp816Val variant or aberrant expression of CD25 or CD2 on MC. The 2 primary groups of MCAS are mastocytosis (cutaneous and systemic [SM]) and monoclonal MCAS. Patients with mastocytosis should fulfill the World Health Organization diagnostic criteria for this disorder. Diagnosis requires the major plus one minor criterion or 3 minor createria.
The consensus diagnostic creteria for SM include: 
Major criterion: 
- Imaging of the multifocal infiltrates
Minor criteria:
- Identifying morphological features of above 25% of MC from bone marrow biopsy.
- Detection of the point alteration at codon 816 in the KIT gene.
- CD2, CD25, and/or CD30 expression in MC
- Persistently elevated serum tryptase (>20 ng/mL)

The 2 main nonclonal MCAS categories include secondary MCAS, for which there is a known trigger for MC activation (IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes), and idiopathic, in which the etiology for MC activation is undefined. Based on consensus criteria, the diagnosis of MCAS can be established when typical clinical symptoms arising from recurrent (episodic) acute systemic MC activation (typically in the form of recurrent anaphylazis in at least 2 organ systems) have been documented; MC-derived mediators increase substantially in serum or urine over the individual's baseline; and the symptoms respond to drug blocking MC activation, MC mediators, mediator production, or mediator effects.

A recently proposed diagnostic algorithm for the elevation of patients with suspected MCAS considers 2 main diagnoses that may underlie severe forms of MC activation (anaphylaxis), namely, IgE-dependent allergies and clonal MC disorders. A serum tryptase level, which has been used in diagnosing these disorders, has several drawbacks, including the need to obtain acute and baseline tryptase level has been reported in hereditary alpha tryptasemia, complicating the diagnostic possibilities. In addition to the limitations of serum tryptase, there are reports of symptomatic patients with features of MC activation who do not meet all the criteria for MCAS but have elevated baseline mediator metabolites. In these pateints, there is evidenc ethat their symptoms respond to drugs that target MC activation, the mediators released by MC, and/or the effects of these mediators. Based on these observations, validated biomarkers suggestive of MC activation, such as an increase in the histamine metabolite (N-methylhistamine) or the prostaglandin D2 metabolite (2,3-Dinor 11-Beta-Prostaglanding F2 alpha), have been recommended for testing when tryptase is not available, or the results is inconclusive. 

With respect to urine LTE4, there is increasing clinical evidencce for its use in patients at risk for aspirin intolerance in asthma (asprin-exacerbated respiratory disease) and other forms of asthma. For example, elevated LTE4 concentrations have been shown to correlate with traditional markers and represent a noninvasive approach to asthma phenotyping in patients with type 2 asthma mediated in part by MC and eosinophils. In this study, increased urine LTE4 levels were associated with lower lung unction and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in adult and adolescent patients wtih asthma. Based on these and other findings, there is interest for the use of therapeutics that target the production of inflammatory eicosanoids, such as LTE4, in the management of these diseases.