Immunohistochemical differentiation of eosinophilic esophageal myositis from eosinophilic esophagitis.
OBJECTIVE
Eosinophilic esophagitis (EoE) is a Th2-mediated allergic disease of the esophageal epithelium, associated with antigen. We previously reported a case series for eosinophilic esophageal myositis (EoEM)-a novel eosinophilic gastrointestinal disorder defined as eosinophilic infiltration localized in the esophageal muscle layer-and diagnosed it by peroral endoscopic muscle biopsy. Here, we investigated the immunopathology of EoEM to differentiate it from EoE.


METHODS
Histological analysis was performed for three cases of EoEM and EoE, respectively. The results were compared with those of two control samples (non-eosinophilic gastrointestinal disorder full-layer esophagus). Using immunofluorescence, we analyzed the expression of the chemokine receptor CCR3 and its ligands eotaxin-1 and eotaxin-3 to investigate the eosinophilic reaction. Additionally, we determined the expression patterns of desmoglein-1 in the esophageal epithelium, which shows dysregulated expression in EoE.


RESULTS
Eosinophil infiltration was observed in the muscle layer (maximum number, 30, 36, 73/high-power field) and the epithelium (50, 44, 40/high-power field) for EoEM and EoE, respectively. In EoE esophageal epithelium, the number of eotaxin-3-positive epithelial cells was significantly increased together with CCR3-positive infiltrating cells. However, in EoEM, a number of eotaxin-1-positive and eotaxin-3-positive myocytes and vascular endothelial cells were increased in the esophageal muscle layer. A significant loss of desmoglein-1 expression was only observed in EoE, not in EoEM.


CONCLUSIONS
Eotaxin-1 and eotaxin-3 expression on the smooth muscle and vessels plays a role in the pathogenesis of EoEM, while EoE shows an epithelial eotaxin-3-dominant immunoreaction. Thus, the EoEM immunological pattern displays clear differences from that of EoE.
Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.
Hiroki
H
Sato
Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.
Nao
N
Nakajima
Division of Cellular and Molecular Pathology, Department of Cellular Function, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Go
G
Hasegawa
Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.
Yuzo
Y
Kawata
Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.
Yuichi
Y
Sato
Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.
Kenji
K
Suzuki
Division of Gastroenterology and Hepatology, Saiseikai Niigata Daini Hospital, Niigata, Japan.
Terasu
T
Honma
Division of Gastroenterology and Hepatology, Niigata University Medical and Dental Hospital, Niigata, Japan.
Shuji
S
Terai
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D054413:Chemokine CCL11 / Q000032:analysis; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000032:analysis; D003937:Diagnosis, Differential; D016099:Endoscopy, Gastrointestinal; D057765:Eosinophilic Esophagitis / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology*; D004935:Esophageal Diseases / Q000175:diagnosis* / Q000473:pathology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D049288:Muscular Dystrophies, Limb-Girdle / Q000175:diagnosis* / Q000473:pathology*; D054397:Receptors, CCR3 / Q000032:analysis; D018418:Th2 Cells / Q000276:immunology
D015415:Biomarkers; C515456:CCL11 protein, human; C120429:CCL26 protein, human; D054413:Chemokine CCL11; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D054397:Receptors, CCR3
CCR3; desmoglein-1; eosinophilic esophagitis; eotaxin-1; eotaxin-3