Professionals

EUREOS Guidelines

Non-invasive biomarkers of eosinophilic esophagitis

Eosinophilic gastrointestinal disorders (EGIDs) are emerging inflammatory diseases which may involve any part of the gastrointestinal (GI) tract and lead to the eosinophilic mucosal infiltration in the absence of secondary causes of intestinal eosinophilia (1, 2). Based on the site of the eosinophil inflammations, EGIDs are classified into eosinophilic esophagitis (EoE) and nonesophageal EGIDs (1). While nonesophageal EGIDs still represent a clinical enigma for clinicians, EoE is considered the prototype of EGIDs with standardized guidelines (1, 3). EoE is a chronic/remittent, allergen-mediated disease characterized by esophageal dysfunction and eosinophilic infiltration, affecting both children and adults, with a male-female ratio of 3:1 (4). The prevalence of EoE is significantly increased in the last decade; indeed, it is currently considered one of the most common causes of upper gastrointestinal morbidity (4,5). EoE diagnosis requires 15 eosinophils per high power field in tissue biopsies endoscopically obtained, without concomitant eosinophilic infiltration in other GI tracts (3). To date, the GI endoscopy is the gold standard for the diagnosis and follow-up of patients with EGIDs. The need for several endoscopies to monitor the disease and the absence of validated non-invasive biomarkers or tools are the main reasons for a significant burden on affected patients and the healthcare system (6). Therefore, there is a critical need for non-invasive biomarkers to replace such invasive monitoring. Several efforts have been made to identify potential non-invasive biomarkers for diagnosing and monitoring the disease in the last years.

Recently Votto et al. published a review showing promising non-invasive biomarkers for diagnosing and monitoring EGIDs, despite none of these have been incorporated into guideline recommendations. Absolute eosinophil count, circulating eosinophil progenitors, and eosinophil granule proteins (eosinophil cationic protein [ECP], eosinophil-derived neurotoxin [EDN], eosinophil peroxidase [EPX]), and galectin-10 (GAL-10) have been identified as the most specific biomarkers of active EoE, especially if used in combination. In a recent pediatric case-control study, Wechsler et al. showed that plasma GAL-10, ECP, EDN, Eotaxin-3, major basic protein-1 (MBP-1) are significantly increased in EoE compared to healthy controls. Thus, the combination of this novel panel of eosinophil-associated proteins results as a potential non-invasive tool to identify untreated EoE patients from non-EoE controls.

Furthermore, several studies reported that EoE patients had a marked change in tissue-specific gene expression. Lu et al. investigated esophageal miRNA expression profile in patients with active disease and responsive to steroids, finding that the expression levels of specific miRNAs (miR-21, miR-223, and miR-375) strongly correlated with esophageal eosinophil levels (7). Other epigenetic mechanisms such as DNA methylation have been recently assessed. Pediatric patients with EoE showed differences in mucosal DNA methylation profiles compared to controls (8).

EoE is a multifactorial disease. Although recent evidence suggested a fundamental pathogenetic role of the environmental factors, several studies have also reported that genetic predisposition is a significant risk factor in the development of EoE (9). Different studies, including candidate-gene identification and genome-wide association studies, have identified gene loci that have been associated explicitly with EoE (10). In this context, the Cincinnati Children's Hospital researchers developed a specific diagnostic panel comprising a 96-gene quantitative PCR array to identify patients with EoE monitor the disease and response to therapy (11).

The future of EGIDs is exciting from both a diagnostic and therapeutic standpoint. The growing number of genetic, molecular expression, and immunologic analyses, in conjunction with increased differentiation of clinical phenotypes and biomarker-supported endotypes, will help clinicians explain differing therapeutic responses, predict clinical response, guide individual therapies, and improve patient outcomes. Therefore, further research is required to confirm phenotypes and histological or serological biomarkers to provide a novel endotype classification based on different cytokine or genetic signatures.

Summary
Votto Martina, De Filippo Maria, Marseglia Gian Luigi and Licari Amelia; 
Pediatric Unit, Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy 

Votto et al., Acta Biomed. 2021 Nov 29;92(S7):e2021530. doi: 10.23750/abm.v92iS7.12401.

 

References

1. Licari A, Votto M, D'Auria E, et al. Eosinophilic Gastrointestinal Diseases in Children: A Practical Review. Curr Pediatr Rev. 2020;16(2):106-114.

2. Licari A, Votto M, Scudeller L, et al. Epidemiology of Nonesophageal Eosinophilic Gastrointestinal Diseases in Symptomatic Patients: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2020;8(6):1994-2003.

3. Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the AGREE Conference. Gastroenterology. 2018;155(4):1022-1033.

4. Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015;373(17):1640-8.

5. Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018;154(2):319-332.

6. Votto M, Castagnoli R, De Filippo M, et al. Behavioral issues and quality of life in children with eosinophilic esophagitis. Minerva Pediatr. 2020;72(5):424-432.

7. Lu TX, Sherrill JD, Wen T, et al. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2019;129(4):1064-1075. 

8. Strisciuglio C, Payne F, Nayak K, et al. Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis. Clin Epigenetics. 2021;13(1):81.

9. Votto M, Marseglia GL, De Filippo M, et al. Early Life Risk Factors in Pediatric EoE: Could We Prevent This Modern Disease? Front Pediatr. 2020;8:263.

10. O'Shea KM, Aceves SS, Dellon ES, et al. Pathophysiology of Eosinophilic Esophagitis. Gastroenterology. 2018;154(2):333-345. 

11. Wen T, Rothenberg ME. Clinical Applications of the Eosinophilic Esophagitis Diagnostic Panel. Front Med (Lausanne). 2017;4:108.

Go back

Copyright 2024. All Rights Reserved.
Settings saved
Datenschutzeinstellungen

Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Aenean commodo ligula eget dolor. Aenean massa. Cum sociis natoque penatibus et magnis dis parturient montes.

Dies sind Blindinhalte in jeglicher Hinsicht. Bitte ersetzen Sie diese Inhalte durch Ihre eigenen Inhalte. Lorem ipsum dolor sit amet, consectetuer adipiscing elit. Aenean commodo.

user_privacy_settings

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert die Privacy Level Einstellungen aus dem Cookie Consent Tool "Privacy Manager".

user_privacy_settings_expires

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert die Speicherdauer der Privacy Level Einstellungen aus dem Cookie Consent Tool "Privacy Manager".

ce_popup_isClosed

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert, dass das Popup (Inhaltselement - Popup) durch einen Klick des Benutzers geschlossen wurde.

onepage_animate

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert, dass der Scrollscript für die Onepage Navigation gestartet wurde.

onepage_position

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert die Offset-Position für die Onepage Navigation.

onepage_active

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert, dass die aktuelle Seite eine "Onepage" Seite ist.

view_isGrid

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert die gewählte Listen/Grid Ansicht in der Demo CarDealer / CustomCatalog List.

portfolio_MODULE_ID

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert den gewählten Filter des Portfoliofilters.

Eclipse.outdated-browser: "confirmed"

Domainname: Domain hier eintragen
Ablauf: 30 Tage
Speicherort: Localstorage
Beschreibung: Speichert den Zustand der Hinweisleiste "Outdated Browser".
You are using an outdated browser. The website may not be displayed correctly. Close