Clinical Information

Leukotrienes (LTs) 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 (cys-LT) production. Assessment of LTE4 in urine allows for noninvasive specimen collection and avoids artifactual formation of LTs during phlebotomy. Generation of LTE4 occurs nonspecifically from active mast cells, basophils, eosinophils, and macrophages, and modulated through a variety of mechanisms. Elevated concentrations of LTE4 are associated with inflammatory and accelerated mast cell activation conditions, specifically in patients with systemic mast cell disease.(1)

Systemic mastocytosis (SM), or systemic mast cell disease, is a myeloproliferative neoplasm which has infiltrated extracutaneous organs. Release of mast cell inflammatory mediators leads to disease symptoms including those associated with allergic and anaphylactic reactions, while increased mast cell number leads to organ dysfunction. Consensus diagnostic criteria for SM include 1 major criterion: imaging of the multifocal infiltrates; and 4 minor criteria: 1) identifying morphological features of >25% of mast cells from bone marrow biopsy, 2) detection of the point mutation at codon 816 in the KIT gene, 3) CD2 and/or CD25 expression in mast cells, and 4) persistently elevated serum tryptase. Diagnosis requires either 1 major plus 1 minor criterion or 3 minor criteria.(2)

Measurement of urinary mast cell activation biomarkers can aid in the initial evaluation of suspected cases of systemic mast cell disease, potentially avoiding the need for imaging and bone marrow examination. Patients with SM frequently have elevated urine concentrations of LTE4(1), N-methylhistamine(3,4), and/or 2,3-dinor 11 beta-prostaglandin F2 alpha.(4)

Urinary LTE4 has also demonstrated significant utility in patients with asthma and respiratory diseases. In a study of adults with mild to moderate asthma on 5-lipoxygenase inhibitors, urine LTE4 concentrations decreased approximately 40% compared to asthma control subjects, suggesting modest decreases in LTE4 production correlates with clinical improvements in asthma severity.