Biomarker For Eosinophilic Esophagitis Research Articles

169 – Interleukin-13-Mediated Release of Mitochondrial Dna from Esophageal Epithelial Cells: A Novel Biomarker for Eosinophilic Esophagitis

169 – Interleukin-13-Mediated Release of Mitochondrial Dna from Esophageal Epithelial Cells: A Novel Biomarker for Eosinophilic Esophagitis

Serum Biomarkers for the Diagnosis of Eosinophilic Esophagitis and Eosinophilic Gastroenteritis.

Objective Clinically useful serum biomarkers for the diagnosis and monitoring of eosinophilic gastrointestinal diseases are not available. This study was conducted to examine the possible value of eosinophil-related proteins as serum biomarkers. Methods The serum concentrations of 49 cytokines, chemokines, and other proteins were measured in 29 patients with eosinophilic gastrointestinal diseases and 80 controls. Results The levels of interleukin (IL)-5, IL-33, eotaxin-3, and thymic stromal lymphopoietin (TSLP), previously reported as possible biomarkers of eosinophilic esophagitis, were not significantly elevated in the serum. In contrast, the B cell-attracting chemokine (BCA)-1/chemokine (C-X-C motif) ligand (CXCL) 13 and hemofiltrate C-C chemokine (HCC)-1/CC chemokine ligand (CCL) 14α levels were significantly elevated, while the granulocyte chemotactic protein (GCP)-2/CXCL6 levels were suppressed in patients with eosinophilic esophagitis as well as in those with eosinophilic gastroenteritis. The cutaneus T cell-attracting chemokine (CTACK)/CCL27, stromal cell-derived factor (SDF)-1/CXCL12, macrophage inflammatory protein (MIP)-3β/CCL19, and squamous cell carcinoma antigen (SCCA) 2 levels were elevated only in patients with eosinophilic esophagitis. However, there were large overlaps of data obtained from the patient and control groups, indicating that these serum biomarkers are not adequately sensitive for clinical use with presently available assay systems. Conclusion Of the 49 investigated serum proteins, none were shown to be adequately sensitive for use as biomarkers for the diagnosis or monitoring of eosinophilic gastrointestinal diseases.

Biomarkers for Eosinophilic Esophagitis: A Systematic Review

Diagnosis and monitoring of response to treatment in eosinophilic esophagitis (EoE) continue to be challenging, especially due to lack of a definitive biomarker. The aim of this study was to review the literature on various biomarkers of EoE.

Marked Deposition of Eosinophil-Derived Neurotoxin in Adult Patients With Eosinophilic Esophagitis (Am J Gastroenterol 2010;105:298-307)

A study about eosinophil-derived neurotoxin (EDN) as a biomarker for eosinophilic esophagitis (EoE) has been reported in the February issue of Am J Gastroenterology 2010.1 A diagnostic hallmark of EoE is the number of eosinophils infiltrated in the esophageal epithelium, but there seems to be no universal agreement on either the number or the location of eosinophils required to diagnose EoE. Although the role of eosinophils in the pathophysiology of EoE is not fully understood, eosinophils have a key role in eosinophil related gastrointestinal disease. Therefore eosinophil granule protein and EDN released by eosinophils, and eotaxin-3 have been studied as other possible biomarkers of EoE. Blood, urine or tissue levels of eosinophil granule proteins and EDN are elevated in eosinophilic associated diseases.2-6 However, information regarding localization of EDN in the diseased tissues has not been available. The authors investigated tissue specimens from 10 adult EoE patients and 8 histologically normal controls. Using a polycloncal rabbit antibody to EDN, sections from mid-esophageal biopsy specimens were stained for EDN by immunofluorescence. Cellular staining (infiltration of intact eosinophils) and extracellular staining (deposition of released EDN) were scored in a blinded manner on an established 7-point scale. In the results, esophageal biopsy specimens from normal controls showed no or few intact eosinophils and extracellular EDN depositions. In contrast, EDN staining was clearly observed in specimens from all EoE patients. In some EoE patients, marked extracellular EDN deposition was observed despite a relatively small numbers of intact eosinophils. And there was no correlation between the eosinophil infiltration and the extracellular EDN staining scores. They concluded that tissue eosinophil counts might underestimate how extensively eosinophils are involved, particularly in individuals with marked eosinophil degranulation. Evaluation of EDN in esophageal biopsy specimens was suggested as an useful mean to diagnose and manage patients with EoE.

Marked deposition of eosinophil-derived neurotoxin in adult patients with eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is characterized by infiltration of eosinophils into esophageal epithelium. Blood levels of an eosinophil granule protein, eosinophil-derived neurotoxin (EDN), have been proposed as a biomarker for EoE. However, information regarding localization of EDN in the diseased tissues has not been available. The goal of this study was to evaluate the magnitude and distribution of EDN deposition in tissue specimens from the esophagus of EoE patients. We studied specimens from 10 adult EoE patients and eight histologically normal controls (three under age 17). Sections from mid-esophageal biopsy specimens were stained for EDN by immunofluorescence, using a polyclonal rabbit antibody to EDN. Cellular staining (i.e., infiltration of intact eosinophils) and extracellular staining (i.e., deposition of released EDN) were scored in a blinded manner on an established 7-point scale. Esophageal biopsy specimens from histologically normal controls showed no or few intact eosinophils and no or minimal extracellular EDN deposition. In contrast, EDN staining was clearly observed in specimens from all EoE patients. In some EoE patients, marked extracellular EDN deposition was observed despite relatively small numbers of intact eosinophils. Overall, there was no correlation between the eosinophil infiltration and the extracellular EDN staining scores. Marked tissue deposition of extracellular EDN is present in the esophagus of EoE patients. Tissue eosinophil counts may underestimate how extensively eosinophils are involved, particularly in individuals with marked eosinophil degranulation. Evaluation of EDN staining in esophageal biopsy specimens may be useful to diagnose and manage patients with EoE.

Localization of Eosinophil-Derived Neurotoxin in Esophageal Tissues: A Potential Biomarker for Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is characterized by infiltration of eosinophils into esophageal epithelium. Blood levels of an eosinophil granule protein, eosinophil-derived neurotoxin (EDN), have been proposed as a biomarker for EE. Here, we evaluated the tissue localization of EDN in esophageal epithelium.

Noninvasive Markers of Eosinophilic Esophagitis

There has been an increasing awareness and recognition of eosinophilic esophagitis (EE), a chronic condition with periods of exacerbation and remission, over the last decade. The complex pathophysiology of EE and eosinophil physiology provide several candidate biomarkers that could be studied on various noninvasively obtained body specimens. This article reviews several potential noninvasive biomarkers of EE.

Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis

Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.