Nahoko Nagano1, Asuka Araki2, Noriyoshi Ishikawa1, Mamiko Nagase3, Kyoichi Adachi4, Norihisa Ishimura5, Shunji Ishihara5, Yoshikazu Kinoshita6, Riruke Maruyama3. 1. Pathology Unit, Shimane University Hospital, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan. 2. Organ Pathology Unit, Department of Pathology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan. asuka@med.shimane-u.ac.jp. 3. Organ Pathology Unit, Department of Pathology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan. 4. Shimane Environmental and Health Public Corporation, 1-4-6 Koshibara, Matsue, Shimane, 690-0012, Japan. 5. Department of Gastroenterology and Hepatology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan. 6. Steel Memorial Hirohata Hospital, 3-1 Yumesaki-cho, Hirohata-ku, Himeji, Hyogo, 671-1122, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Rémi Doucet-Ladevèze; Sébastien Holvoet; Frédéric Raymond; Francis Foata; Gurjit K Khurana Hershey; Joseph D Sherrill; Marc E Rothenberg; Carine Blanchard Journal: Front Pediatr Date: 2019-11-20 Impact factor: 3.418