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Elevated levels of leukotriene C4 synthase mRNA distinguish a subpopulation of eosinophilic oesophagitis patients

机译：白三烯C4合酶mRNA水平升高可区分嗜酸性食管炎患者亚群

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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 (LTC4S), 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. LTC4S mRNA levels were quantified in whole blood samples. Leukotriene E4 was measured in urine. Results: LTC4S 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 LTC4S 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. LTC4S 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 LTC4S 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 LTC4S mRNA may facilitate diagnosis of an EoE subpopulation for personalized therapy.
机译：背景：半胱氨酰白三烯有助于Th2型炎症性免疫反应。然而，它们在食管组织中的水平不能将嗜酸性食管炎（EoE）患者与对照患者区分开。目的：我们询问白三烯生产的关键调节剂白三烯C4合酶（LTC4S）的mRNA水平是否可以作为EoE的标记。方法：对30例儿科EoE患者和40例非EoE对照者的近端和远端食管活检进行数字mRNA表达谱分析（nCounter？Technology）。用RT-qPCR确认表达数据。在全血样品中定量LTC4S mRNA水平。在尿液中测量了白三烯E4。结果：EoE患者食管活检的近端（2.6倍，P <0.001）和远端（2.9倍，P <0.001）的LTC4S mRNA水平升高。重要的是，增加的LTC4S mRNA转录物确定了EoE患者的亚群（28％）。该患者亚组的血清IgE水平较高（669 U / mL对106 U / mL，P = 0.01），胸腺基质淋巴细胞生成素（TSLP）（1.6倍，P = 0.009）和CD4（1.4-倍，P ＝ 0.04）但降低IL-23 mRNA水平（0.5倍，P ＝ 0.04）。相反，在反流性食管炎患者的食管活检中发现IL-23 mRNA水平升高。 EoE患者亚组和非EoE患者的全血和白三烯E4尿排泄中的LTC4S mRNA转录物相似。结论与临床意义：在一个EoE患者亚组中发现LTC4S mRNA的食管表达升高，并伴有更高的血清IgE水平和指示更明显的过敏表型的食管转录组。食道LTC4S mRNA与TSLP和IL-23 mRNA水平一起可以促进诊断EoE亚群以进行个性化治疗。

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