May 03, 2018
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3 subtypes of EoE discovered

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Marc E. Rothenberg
Marc E. Rothenberg
Nicholas J. Talley
Nicholas J. Talley

Eosinophilic esophagitis has three distinct subtypes associated with different clinical features and molecular pathways, according to new research published in the Lancet Gastroenterology & Hepatology.

Marc E. Rothenberg, MD, PhD, of the division of allergy and immunology at Cincinnati Children’s Hospital Medical Center, and colleagues said their findings could aid in the development of new targeted drugs to treat this emerging food allergic condition.

“Our goal is to provide the type of deep disease understanding and therapeutic decision-making that is now becoming routine in the cancer field,” Rothenberg said in a press release. “These findings provide a potential framework for developing distinct predictive medicine and future therapeutic strategies for specific EoE subpopulations.”

In a cross-sectional study of 10 hospital sites across the country, Rothenberg and colleagues analyzed biopsies taken from 185 children and adults with EoE, noting various structural and molecular features of each sample.

Using a diagnostic panel comprising 96 molecular targets, the researchers identified three endotypes that were consistent across their study population and independent of the number of eosinophils in each sample. The endotypes —EoEe1, EoEe2 and EoEe3 — ranged from mild to severe.

“We applied deep molecular profiling of biopsy tissues from patients undergoing endoscopy to evaluate the presence of EoE,” Rothenberg said. “We found that molecular profiling provided an advantage compared with classical microscopic analysis, the traditional approach to looking at biopsy specimens.”

In a related commentary published in the Lancet Gastroenterology & Hepatology, Simon Keely, PhD, and Nicholas J. Talley, MD, PhD, both from the University of Newcastle in Australia, wrote that the study could provide insights into the potential development of therapies not just for EoE, but for other gastrointestinal conditions as well.

“Management of gastrointestinal disorders such as [EoE] and inflammatory bowel disease often show scant treatment successes because of the broad grouping of disease based on only pathological features; tailored treatment approaches are an important unmet need for these conditions,” they wrote. “Whether the [eosinophilic esophagitis diagnostic panel] approach for [EoE] will provide better disease management, and whether these endotypes respond differently to targeted treatments, is now of major interest and highlights the need for similar endotyping approaches for other unexplained gut diseases, such as functional gastrointestinal disorders.” – by Alex Young

Disclosures: Rothenberg reports he is a consultant for PulmOne Therapeutics, Spoon Guru, Celgene, AstraZeneca, GlaxoSmithKline, ClostraBio, Merck, Immune Pharmaceuticals, and NKT Therapeutics; he has an equity interest in PulmOne Therapeutics, Spoon Guru, Celgene, and Immune Pharmaceuticals; he also receives royalties from Teva Pharmaceuticals and is an inventor on a patent owned by Cincinnati Children’s Hospital Medical Center. Please see the full study for the other authors’ relevant financial disclosures. Keely reports grants from Commonwealth Diagnostics, Fisher and Paykel Healthcare, and Syntrix Biosystems. Talley reports grants from Abbott Pharmaceuticals, Commonwealth Diagnostics, Janssen, Prometheus, Pfizer, Rome Foundation, Salix, and GI Therapies, as well as personal fees for consultancy from Adelphi Values, GI Therapies, Allergens, Napo Pharmaceutical, Outpost Medicine, Samsung Bioepis, Yuhan, Synergy, and Theravance. He has licensed patents for biomarkers of irritable bowel syndrome, for licensing questionnaires licensed to Mayo and Talley, and for FGIDs. He also has a patent issued for microbiota modulation of BDNF tissue repair pathway