Effects of topical steroids on tight junction proteins and spongiosis in esophageal epithelia of patients with eosinophilic esophagitis

DA Katzka, R Tadi, TC Smyrk, E Katarya… - Clinical …, 2014 - Elsevier
DA Katzka, R Tadi, TC Smyrk, E Katarya, A Sharma, DM Geno, M Camilleri, PG Iyer
Clinical Gastroenterology and Hepatology, 2014Elsevier
Background & Aims The allergic response associated with eosinophilic esophagitis (EoE)
occurs when food antigens permeate tight junction–mediated epithelial dilated intercellular
spaces. We assessed whether levels of tight junction proteins correlate with the dilation of
intercellular spaces (spongiosis) and the effects of topical steroids on these parameters.
Methods We assessed esophageal biopsy samples from 10 patients with active EoE treated
with topical fluticasone, 10 untreated patients, and 10 patients without esophageal disease …
Background & Aims
The allergic response associated with eosinophilic esophagitis (EoE) occurs when food antigens permeate tight junction–mediated epithelial dilated intercellular spaces. We assessed whether levels of tight junction proteins correlate with the dilation of intercellular spaces (spongiosis) and the effects of topical steroids on these parameters.
Methods
We assessed esophageal biopsy samples from 10 patients with active EoE treated with topical fluticasone, 10 untreated patients, and 10 patients without esophageal disease (controls) for degree of spongiosis. Immunohistochemical assays were used to determine the levels of the tight junction proteins filaggrin, zonula occludens (ZO)-1, ZO-2, ZO-3, and claudin-1. Histology and immunohistochemistry results were assessed blindly, with levels of tight junction proteins and degree of spongiosis rated on scales of 0 to 3.
Results
The mean degrees of spongiosis in untreated and treated patients with EoE were 1.3 and 0.4, respectively (P = .016). Esophageal epithelia did not stain significantly for ZO-1 or ZO-2. Filaggrin was observed in a predominant cytoplasmic pattern, compared with the cytoplasmic and membranous patterns of ZO-3 and claudin-1. In biopsy specimens from patients with active EoE, the mean staining intensities for filaggrin, ZO-3, and claudin-1 were 1.6, 1.4, and 0.7, respectively. In biopsy specimens from patients treated with fluticasone, levels of filaggrin, ZO-3, and claudin-1 were 2.8 (P = .002 compared with untreated patients), 1.7 (P = .46 compared with untreated patients), and 1.3 (P = .25 compared with untreated patients), respectively. The correlation between the level of filaggrin and the degree of spongiosis was r = 0.23, and between ZO-3 staining and the degree of spongiosis was r = .016 (P = .001 for filaggrin vs ZO-3 staining).
Conclusions
Filaggrin, ZO-3, and claudin-1 (but not ZO-1 or ZO-2) are detected in the esophageal mucosa of patients with EoE treated with steroids and individuals without esophageal disease. Without treatment, spongiosis increases, corresponding with reduced levels of filaggrin, ZO-3, and claudin-1. Loss of tight junction regulators and dilation of intercellular spaces appear to be involved in the pathophysiology of EoE and could be targets for treatment.
Elsevier