Subepithelial collagen deposition, profibrogenic cytokine gene expression, and changes after prolonged fluticasone propionate treatment in adult eosinophilic esophagitis: A?prospective study

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• 作者：Alfredo J. Lucendo MD ; PhD ; FEBG^a ;   ; ^{alucendo@vodafone.es} ; Á ; ngel Arias BSc^b ; Livia C. De Rezende MD ; PhD^a ; Jose Luis Yagü ; e-Compadre MD^c ; Teresa Mota-Huertas APT^c ; Sonia Gonzá ; lez-Castillo MD^a ; Rubé ; n A. Cuesta MD^c ; José ; M. Tenias MD ; PhD^b ; Teresa Belló ; n PhD^d
• 关键词：Eosinophilic esophagitis ; fibrosis ; lamina propria ; IL-5 ; TGF-¦Â1 ; fibroblast growth factor 9 ; CCL18 ; fluticasone propionate
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2011
• 出版时间：November 2011
• 年：2011
• 卷：128
• 期：5
• 页码：1037-1046
• 全文大小：2332 K

文摘

Background

Recent research shows that both pediatric and adult patients with eosinophilic esophagitis (EoE) experience esophageal remodeling marked by increased collagen deposition in which TGF-¦Â plays an important role. However, limited data are available on the intensity and reversibility of fibrous remodeling in adults with EoE.

Objective

We sought to analyze differences in collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene expression along with other changes induced by prolonged treatment with fluticasone propionate in adults with EoE.

Methods

Ten adults given consecutive diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens were obtained before and after 1 year of treatment with fluticasone propionate. Collagen deposition in the LP was assessed in tissue sections with the aid of the Masson trichrome technique. IL5, TGFB1, fibroblast growth factor 9 (FGF9), and CCL18 gene expression was quantified through real-time PCR. EoE results were compared among samples from 10 adult patients with gastroesophageal reflux disease and 10 control subjects with healthy esophagi.

Results

Patients with EoE showed a significant increase in subepithelial collagen deposition; this correlated positively with eosinophil density in the LP and the patient¡¯s age. Prolonged steroid treatment induced a nonsignificant reduction in subepithelial fibrosis, which remained significantly higher than in control subjects. Profibrogenic cytokine gene expression also increased in patients with EoE, with IL5 (P?< .001), FGF9 (P?=?.005), and CCL18 (P?= .008) all significantly upregulated. After 1 year of treatment, a reduction was observed in gene expression; for CCL18 expression, this decrease was statistically significant (P?< .001).

Conclusions

Esophageal remodeling is associated with upregulated gene expression of profibrogenic cytokines in adults with EoE. Prolonged treatment with fluticasone propionate leads to a nonsignificant reduction in subepithelial collagen deposition accompanied by downregulation of profibrogenic cytokine gene expression, with that of CCL18 being especially significant.