| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1968437 | Clinical Biochemistry | 2016 | 4 Pages |
•The analytical and clinical performance of an LC–MS/MS method to measure urinary leukotriene E4 (LTE4) is described.•Normal reference values for urinary LTE4, 11β-prostaglandin F2α, and N-methyl histamine are not influenced by age or gender.•Urine LTE4 identifies patients with systemic mastocytosis among patients with diverse allergic disease presentations.
ObjectivesSystemic mastocytosis (SM) is a disorder characterized by the excessive accumulation of clonally derived mast cells in various tissues. When triggered, mast cells release large amounts of histamine, prostaglandins and leukotrienes. Leukotriene E4 (LTE4) is the primary stable metabolite of total cysteinyl leukotrienes. We hypothesized that secretion of LTE4 would be increased in SM and could be used alone or in combination with current urinary biomarkers to optimize screening for SM.Design and methodsLTE4 was measured by liquid chromatography followed by tandem mass spectrometry (LC–MS/MS). Analytical assay validation was performed using residual urine specimens. LTE4 results were normalized to urine creatinine for clinical use. Reference interval was established using a healthy volunteer cohort. Clinical sensitivity and specificity for SM detection were determined by measuring urinary biomarkers (LTE4, N-methyl histamine [NMH] and 11β-prostaglandin F2α [BPG]) in a cohort of 409 patients referred to allergy specialists, 66 (16%) of which were diagnosed with SM.ResultsUrinary LTE4 measurement was accurate, precise and linear across a range of 31–3020 pg/mL. The 95th percentile of the reference interval population was < 104 pg/mg creatinine. Median urine LTE4 concentrations were significantly higher among patients with SM (97 pg/mg cr. vs. 50 pg/mg cr.; p < 0.01). Elevated urinary LTE4 was 48% sensitive and 84% specific for SM. Clinical sensitivity was 53% for BPG (> 1000 ng/mL) and 71% for NMH (> 200 ng/mL). Incorporating all three urinary metabolites improved the SM diagnostic sensitivity to 97%, with minimal change in specificity.ConclusionsWe have developed a sensitive and precise LC–MS/MS assay for quantitation of LTE4 in urine. Incorporating LTE4 into a panel including BPG and NMH provides a much-needed screening tool for a complicated disease with non-specific symptoms and invasive confirmatory testing.
