We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.

These data demonstrate that the eosinophils from the esophagus of subjects with EoE have increased HLA-DR expression within this tissue.

BackgroundEosinophilic esophagitis (EoE) is characterized by the inflammation of the esophagus and the infiltration of eosinophils into the esophagus, leading to symptoms such as dysphagia and stricture formation. Systemic immune indicators like eotaxin and fibroblast growth factor were evaluated for possible synergistic pathological effects. Moreover, blood cells, local tissue, and plasma from EoE and control subjects were studied to determine if the localized disease was associated with a systemic effect that correlated with presence of EoE disease.MethodReal-time polymerase chain reaction from peripheral blood mononuclear cells (PBMC), immunohistochemistry from local esophageal biopsies, fluid assays on plasma, and fluorescence-activated cell sorting on peripheral blood cells from subjects were used to study the systemic immune indicators in newly diagnosed EoE (n = 35), treated EoE (n = 9), Gastroesophageal reflux disease (GERD) (n = 8), ulcerative colitis (n = 5), Crohn's disease (n = 5), and healthy controls (n = 8).ResultOf the transcripts tested for possible immune indicators, we found extracellular signal-regulated kinase (ERK), Bcl-2, bFGF (basic fibroblast growth factor), and eotaxin levels were highly upregulated in PBMC and associated with disease presence of EoE. Increased FGF detected by immunohistochemistry in esophageal tissues and in PBMC was correlated with low levels of pro-apoptotic factors (Fas, Caspase 8) in PBMC from EoE subjects. Plasma-derived bFGF was shown to be the most elevated and most specific in EoE subjects in comparison to healthy controls and disease control subjects.ConclusionWe describe for the first time a possible mechanism by which increased FGF is associated with inhibiting apoptosis in local esophageal tissues of EoE subjects as compared to controls. Eotaxin and FGF signaling pathways share activation through the ERK pathway; together, they could act to increase eosinophil activation and prolong the half-life of eosinophils in local tissues of the esophagus in EoE subjects.

Background and Aim Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder characterized by upper gastrointestinal symptoms and the presence of high numbers of eosinophils in the esophagus. Although eosinophils in the esophagus have been found to be activated in subjects with EoE, detailed studies of intracellular signaling pathways involved in the mechanism of activation of eosinophils in EoE have heretofore been limited. The aim of the study was to assess whether any surface molecules or transcription factors are activated in peripheral eosinophils in subjects with EoE. Methods Eosinophils and CD3+ lymphocytes were identified directly from 50 μL of whole blood of EoE and control subjects. Using Hi-FACS, levels of surface activation markers, including CD66b, and intracellular phosphoepitopes, including phosphorylated forms of signal transducer and activator of transcription (phospho-STAT) 1 and 6, were measured within each cell subset. Results Levels of surface CD66b as well as levels of intracellular phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were significantly higher for untreated subjects with EoE vs healthy controls (P <0.05). Levels of phospho-STAT1 and phospho-STAT6 in peripheral blood eosinophils were lower in subjects with EoE on therapy versus untreated subjects with EoE (P <0.05). Conclusions Levels of phospho-STAT1 and phospho-STAT6, transcription factors involved in inflammatory processes, were both significantly higher in peripheral eosinophils from untreated (ie, newly diagnosed) subjects with EoE versus subjects with EoE on therapy, healthy controls. Blood-based measurements of CD66b and phospho-STAT levels in peripheral eosinophils may be beneficial for identifying EoE.

A 17-year-old male presented to his primary care physician with a 2-week history of epigastric pain. The pain was localized, burning, temporarily relieved by meals, and occasionally awakened him from sleep. He denied fever, chills, cough, vomiting, or changes in bowel habits. He also denied use of nonsteroidal anti-inflammatory drugs, illicit drugs, or alcohol. There was no history of travel or trauma. His physical examination was remarkable only for epigastric tenderness. Laboratory values including complete blood count (CBC), chemistry, liver panel, erythrocyte sedimentation rate (ESR) and serum Helicobacter pylori immunoglobulin G (IgG) were negative. He was empirically treated with omeprazole. However, his pain progressed in severity and he avoided oral intake. An abdominal ultrasound was normal. Upper endoscopy showed irregular, ulcerated folds extending from the gastroesophageal junction to the antrum ( Fig. 1). Biopsies showed chronic active gastritis with poorly formed granulomas with central necrosis (Fig. 2). Hematoxylin and eosin (H&E) and Giemsa stains were negative for H. pylori. Acid fast bacilli (AFB), periodic acid-Schiff (PAS), and Gomori methenamine silver (GMS) stains were negative for mycobacteria and fungi.After having lost 10 pounds in 10 days, he was referred to our center for further evaluation. He developed hematemesis, which lowered his hematocrit level to 30.4%. ESR had elevated to 33 and C-reactive protein (CRP) was 7.6 mg/l. An urgent upper endoscopy revealed friable tissue, multiple nodules, ulcers throughout the stomach, and active bleeding. The esophagus and duodenum were normal. Biopsies showed poorly formed granulomas with central necrosis. Viral cultures, cytomegalovirus (CMV) polymerase chain reaction, AFB stain, and H. pylori were negative. Extensive workup, including tuberculin skin test, blood culture, rapid plasma reagin for syphilis, human immunodeficiency virus test, histoplasma antibody, screen Brucella antibody, antinuclear antibody, angiotensin-converting enzyme, chronic granulomatous disease test, and celiac panel were negative. Stool studies, including ova and parasites, culture, H. pylori antigen, and Clostridium difficile were negative. Chest X-ray was normal and abdominal computed tomography scan showed thickening and inflammation of the stomach and proximal duodenum. Upper gastrointestinal series with small bowel followthrough barium study showed mucosal disease in the distal esophagus, stomach, distal ileum, and proximal colon. Colonoscopy was normal except for lymphoid nodular hyperplasia. Biopsies were normal. He improved clinically with a protein pump inhibitor (PPI) and iron as his only medications.Three months later, he was seen in clinic for a follow-up visit. He remained asymptomatic, had regained his weight, and his hematocrit and ESR had normalized. He continued to take once daily PPI. A surveillance upper endoscopy showed normal mucosa throughout but biopsies showed

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2016-12-24T18:13:07