Elevated levels of leukotriene C4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patients. Issue 8 (29th July 2013)

• Record Type: Journal Article
• Authors: Lexmond, W. S.; Pardo, M.; Rooney, K.; Goettel, J. A.; Snapper, S. B.; Yen, E. H.; Dehlink, E.; Nurko, S.; Fiebiger, E.
• Is Part Of: Clinical & experimental allergy. Volume 43:Issue 8(2013:Aug.)
• Page Start: 902
• Page End: 913
• Publication Date: 2013-07-29
• Subjects: arachidonic acid metabolism -- eosinophilic gastrointestinal diseases -- leukotriene -- reflux oesophagitis -- Th2 immune response; Allergy -- Periodicals; Immunology -- Periodicals; 616.97
• DOI: 10.1111/cea.12146
• Languages: English
• ISSNs: 0954-7894

Abstract

Summary: Background: Cysteinyl leukotrienes contribute to Th2‐type inflammatory immune responses. Their levels in oesophageal tissue, however, do not distinguish patients with eosinophilic oesophagitis (EoE) from controls. Objective: We asked whether mRNA levels of leukotriene C4 synthase (LTC4 S), a key regulator of leukotriene production, could serve as a marker for EoE. Methods: Digital mRNA expression profiling (nCounter ® Technology) was performed on proximal and distal oesophageal biopsies of 30 paediatric EoE patients and 40 non‐EoE controls. Expression data were confirmed with RT‐qPCR. LTC4 S mRNA levels were quantified in whole blood samples. Leukotriene E4 was measured in urine. Results: LTC4 S mRNA levels were elevated in proximal (2.6‐fold, P < 0.001) and distal (2.9‐fold, P < 0.001) oesophageal biopsies from EoE patients. Importantly, increased LTC4 S mRNA transcripts identified a subpopulation of EoE patients (28%). This patient subgroup had higher serum IgE levels (669 U/mL vs. 106 U/mL, P = 0.01), higher mRNA transcript numbers of thymic stromal lymphopoietin (TSLP) (1.6‐fold, P = 0.009) and CD4 (1.4‐fold, P = 0.04) but lower IL‐23 mRNA levels (0.5‐fold, P = 0.04). In contrast, elevated levels of IL‐23 mRNA were found in oesophageal biopsies of patients with reflux oesophagitis. LTC4 S mRNA transcripts in whole blood and urinary excretion of leukotriene E4 were similar in EoE patient subgroups and non‐EoE patients. Conclusion & Clinical Relevance: Elevated oesophageal expression of LTC4 S mRNA is found in a subgroup of EoE patients, concomitant with higher serum IgE levels and an oesophageal transcriptome indicative of a more‐pronounced allergic phenotype. Together with TSLP and IL‐23 mRNA levels, oesophageal LTC4 S mRNA may facilitate diagnosis of an EoE subpopulation for personalized therapy.