Dataset Information

A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis.

ABSTRACT:

Background & aims

Eosinophilic esophagitis (EoE) is characterized by medically/surgically-resistant gastroesophageal reflux symptoms and dense squamous eosinophilia. Studies suggest that histologic assessment of esophageal eosinophilia alone cannot reliably separate patients with EoE from those with gastroesophageal reflux disease (GERD). Our goal was to develop an assay to identify EoE patients and perhaps differentiate EoE from other causes of esophageal eosinophilia.

Methods

A monoclonal antibody specific for an eosinophil secondary granule protein (eosinophil peroxidase [EPX]) was developed and shown to specifically identify intact eosinophils and detect eosinophil degranulation in formalin-fixed specimens. A histopathologic scoring algorithm was developed to analyze data from patient evaluations; the utility of this algorithm was assessed by using archived esophageal tissues from patients with known diagnoses of EoE and GERD as well as controls from 2 tertiary care centers.

Results

Intraobserver/interobserver blinded evaluations demonstrated a significant difference (P < .001) between scores of samples taken from control subjects, from patients with esophageal eosinophilia who had a diagnosis of EoE, and from patients with GERD (P < .001). This algorithm also was able to identify patients whose clinical course was suggestive of a diagnosis of EoE, but that nonetheless failed to reach the critical threshold number of > or =15 eosinophils in a high-power (40x) microscopy field.

Conclusions

A novel immunohistochemical scoring system was developed to address an unmet medical need to differentiate histologic specimens from patients with EoE relative to those with GERD. The availability of a unique anti-EPX-specific monoclonal antibody, combined with the ease/rapidity of this staining method and scoring system, will provide a valuable strategy for the assessment of esophageal eosinophilia.

SUBMITTER: Protheroe C

PROVIDER: S-EPMC2706311 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis.

Protheroe Cheryl C Woodruff Samantha A SA de Petris Giovanni G Mukkada Vince V Ochkur Sergei I SI Janarthanan Sailajah S Lewis John C JC Pasha Shabana S Lunsford Tisha T Harris Lucinda L Sharma Virender K VK McGarry Michael P MP Lee Nancy A NA Furuta Glenn T GT Lee James J JJ

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20090401 7

<h4>Background & aims</h4>Eosinophilic esophagitis (EoE) is characterized by medically/surgically-resistant gastroesophageal reflux symptoms and dense squamous eosinophilia. Studies suggest that histologic assessment of esophageal eosinophilia alone cannot reliably separate patients with EoE from those with gastroesophageal reflux disease (GERD). Our goal was to develop an assay to identify EoE patients and perhaps differentiate EoE from other causes of esophageal eosinophilia.<h4>Methods</h4>A ...[more]

PMID: 19345285

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Project description:The characterization of miRNAs and their target mRNAs involved in regulation of the immune process is an area of intense research and relatively little is known governing these processes in allergic inflammation. Here we present novel findings defining the miRNA and mRNA transcriptome in eosinophilic esophagitis (EoE), an increasing recognized allergic disorder.Esophageal epithelial miRNA and mRNA from five paired biopsies pre- and post-treatment with glucocorticosteroids were profiled using Taqman and Affymetrix arrays. Validation was performed on additional paired biopsies, untreated EoE specimens and normal controls. Differentially regulated miRNAs and mRNAs were generated, within which miRNA-mRNA target pairs with high predicted confidence were identified.Compared to the post-glucocorticoid treated esophageal mucosa, of all the 377 miRNA sequences examined, 32 miRNAs were significantly upregulated and four downregulated in the pre-treated biopsies. MiR-214 was the most upregulated (150 fold) and miR-146b-5b, 146a, 145, 142-3p and 21 were upregulated by at least 10 fold. Out of 12 miRNAs chosen for validation by qRT-PCR, five (miR-214, 146b-5p, 146a, 142-3p and 21) were confirmed and 11 shared the same trend. When the expression of the 12 miRNAs in the EoE mucosa was compared to unrelated normal mucosa, six (miR-214, 146b-5p, 146a, 21, 203, and 489) showed similar significant changes as in the paired samples and 10 of them shared the same trend. In the same five pairs of samples used to profile miRNA, 311 mRNAs were down-regulated and 35 were up-regulated in pre-treated EoE mucosa. Among them, 164 mRNAs were identified as potential targets of differentially regulated miRNAs. Further analysis revealed that immune-related genes, targeted and non-targeted by miRNAs, were among the most important genes involved in the pathogenesis of EoE.Our findings add to the accumulating body of data defining a regulatory role for miRNA in immune and allergic processes.

Project description:BACKGROUND AND AIMS:Eosinophilic esophagitis (EoE) is a chronic disorder in children that requires continued assessment of disease activity, involving repeated sedation, endoscopy, and biopsy analysis. We investigated whether mucosal impedance measurements can be used to monitor disease activity in pediatric patients with EoE. METHODS:We measured mucosal impedance at 3 locations in the esophagus in pediatric patients (1-18 years old; 32 with active EoE, 10 with inactive EoE, 32 with nonerosive reflux disease [NERD]) and 53 children with symptoms but normal findings from histologic analyses (controls) undergoing routine esophagogastroduodenoscopy at the Vanderbilt Pediatric Gastroenterology Clinic. Pathologists reviewed biopsies per routine protocol, determined eosinophilic density, and graded spongiosis on an ordinal visual scale. Mucosal impedance measurements were compared within patient groups. The primary outcome was correlation of mucosal impedance measurements with disease activity, based on severity of spongiosis and eosinophil counts. RESULTS:Mucosal impedance measurements were significantly lower in patients with active EoE at 2, 5, and 10?cm above the squamo-columnar junction (median values of 1069, 1368, and 1707, respectively) compared to patients with inactive EoE (median values of 3663, 3657, and 4494, respectively), NERD (median values of 2754, 3243, and 4387), and controls (median values of 3091, 3760, and 4509) (P?<?0.001 for all comparisons to patients with active EoE). We found inverse correlations between mucosal impedance measurements and eosinophil count (P?<?0.001), and spongiosis severity (P?<?0.001). CONCLUSIONS:Mucosal impedance measurements may provide immediate information about mucosal inflammation in children. Patients with active EoE have significantly lower mucosal impedance values than patients with inactive EoE, NERD, or controls; mucosal impedance measurements correlate inversely with eosinophil counts and spongiosis severity. Mucosal impedance is a promising rapid and less-invasive method to monitor EoE activity in pediatric patients with EoE; it could reduce costs and risks of disease monitoring.

Project description:Background & aimsFew factors have been identified that can be used to predict response of patients with eosinophilic esophagitis (EoE) to topical steroid treatment. We aimed to determine whether baseline clinical, endoscopic, histologic, and molecular features of EoE can be used to predict histologic response.MethodsWe collected data from 97 patients with EoE, from 2009 through 2015, treated with a topical steroid for 8 weeks; 59 patients had a histologic response to treatment. Baseline clinicopathologic features and gene expression patterns were compared between patients with a histologic response to treatment (<15 eos/hpf) and non-responders (≥15 eos/hpf). We performed sensitivity analyses for alternative histologic response definitions. Multivariate logistic regression was performed to identify predictive factors associated with response to therapy, which were assessed with area under the receiver operator characteristic (AUROC) curves.ResultsBaseline dilation was the only independent predictor of non-response (odds ratio [OR], 0.30; 95% CI, 0.10-0.89). When an alternate response (<1 eos/hpf) and non-response (<50% decrease in baseline eos/hpf) definition was used, independent predictors of response status were age (OR, 1.08; 95% CI, 1.02-1.14), food allergies (OR, 12.95; 95% CI, 2.20-76.15), baseline dilation (OR, 0.17; 95% CI, 0.03-0.88), edema or decreased vascularity (OR, 0.20; 95% CI, 0.04-1.03), and hiatal hernia (OR, 0.07; 95% CI, 0.01-0.66). Using these 5 factors, we developed a predictive model that discriminated complete responders from non-responders with an AUROC of 0.88. Baseline gene expression patterns were not associated with treatment response and did not change with different histologic response thresholds.ConclusionsIn an analysis of 97 patients with EoE, we found dilation to be the only baseline factor associated with non-response to steroid treatment (<15 eos/hpf). However, a model comprising 5 clinical, endoscopic, and histologic factors identified patients with a complete response (<1 eos/hpf). A baseline gene expression panel was not predictive of treatment response at any threshold.

Dataset Information

A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis.

Background & aims

Methods

Results

Conclusions

Publications

A novel histologic scoring system to evaluate mucosal biopsies from patients with eosinophilic esophagitis.

Similar Datasets

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