Immunohistochemical expression of filaggrin is decreased in proton pump inhibitor non-responders compared with proton pump inhibitor responders of eosinophilic esophagitis.

Abstract

Eosinophilic esophagitis (EoE) is an allergic gastrointestinal disease that features eosinophilic infiltration of esophageal mucosa, but the role of barrier dysfunction of the epithelium in its pathogenesis remains to be elucidated. Clinically, EoE is divided into proton pump inhibitor-non-responders (PPI-NR) and PPI-responders (PPI-R). Our main aims were to investigate the differences of expression of epidermal differential complex (EDC) proteins and desmoglein that are considered to play important roles in formation of the epidermal skin barrier between these two conditions and to seek the usefulness of the differences in pathological diagnosis. Conventional histopathological findings and allergic background were also compared. Twenty-nine PPI-NR and 44 PPI-R were recruited, and 35 reflux esophagitis patients were also enrolled. After clinical information and histopathological findings were reviewed, immunohistochemical expression of EDC proteins (filaggrin, loricrin, and involucrin) and desmoglein in all three groups were examined and semi-quantitatively scored. Regarding allergic conditions, the prevalence of asthma was significantly higher in PPI-NR than in PPI-R. Other allergic conditions showed no differences. Histopathological findings did not exhibit the statistical difference between PPI-NR and PPI-R. However, immunostaining score of filaggrin in PPI-NR was significantly lower than in PPI-R, although the expressions of involucrin, loricrin and desmoglein demonstrated no differences. The results suggest a role of reduced filaggrin expression in the difference of effectiveness of PPI treatment between PPI-NR and PPI-R. Moreover, immunohistochemical determination of filaggrin expression in EoE patients could be informative in the clinical decision of how to treat the patients.