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Elevated levels of leukotriene C 4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patients
Author(s) -
Lexmond W. S.,
Pardo M.,
Rooney K.,
Goettel J. A.,
Snapper S. B.,
Yen E. H.,
Dehlink E.,
Nurko S.,
Fiebiger E.
Publication year - 2013
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12146
Subject(s) - leukotriene c4 , leukotriene , leukotriene e4 , eosinophilic esophagitis , messenger rna , eosinophil , high power field , medicine , immunoglobulin e , immunology , endocrinology , gastroenterology , biology , asthma , immunohistochemistry , antibody , disease , gene , biochemistry
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 C 4 synthase (LTC 4 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 . LTC 4 S mRNA levels were quantified in whole blood samples. Leukotriene E 4 was measured in urine. Results LTC 4 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 LTC 4 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. LTC 4 S mRNA transcripts in whole blood and urinary excretion of leukotriene E 4 were similar in EoE patient subgroups and non‐EoE patients. Conclusion & Clinical Relevance Elevated oesophageal expression of LTC 4 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 LTC 4 S mRNA may facilitate diagnosis of an EoE subpopulation for personalized therapy.