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Molecular Clues Help Distinguish Eosinophilic Colitis and IBD

Graphical abstract summarizing a study on molecular diagnosis of eosinophilic colitis (EoC) and inflammatory bowel disease (IBD). The figure is divided into three sections. The first section illustrates the clinical challenge, showing a colon with eosinophilic inflammation and the statement that EoC and IBD can have overlapping histopathology. The second section outlines the diagnostic workflow: colonic biopsy samples collected from 74 patients at CEGIR sites undergo RNA extraction and qPCR analysis of a 96-gene panel to generate disease-specific molecular scores. The third section presents precision diagnostic results, including receiver operating characteristic (ROC) curves for a 59-gene EoC score and an 18-gene IBD score. The IBD score demonstrates high accuracy in distinguishing active IBD from active EoC. The graphic concludes that the approach supports objective differential diagnosis and accurate identification of IBD in patients with high eosinophil levels. The study was published by Taylor et al. in The Journal of Allergy and Clinical Immunology (2026).

A multicenter Cincinnati Children’s-led study uses gene expression patterns to help distinguish two inflammatory diseases that can appear similar under the microscope

Key Takeaways

  • Eosinophilic colitis (EoC) and inflammatory bowel disease (IBD) can look similar in colon biopsy samples, making diagnosis difficult in some patients. 
  • Researchers developed a gene expression panel that uses molecular signatures in colon tissue to help distinguish EoC from IBD when traditional pathology findings overlap. 
  • The test evaluates two different biological signals: one linked to eosinophilic inflammation and another linked to IBD-associated inflammatory pathways. 
  • By providing information beyond eosinophil counts alone, the approach may help clinicians and pathologists better understand the cause of colonic inflammation in challenging cases. 

 

Diagnosing inflammatory diseases of the colon is not always straightforward. In some patients, eosinophilic colitis (EoC) and inflammatory bowel disease (IBD) can produce similar symptoms and biopsy findings, making it difficult for clinicians and pathologists to determine which condition is present. A study, published on October 28, 2026, in The Journal of Allergy and Clinical Immunology describes a molecular approach designed to add another layer of information to the diagnostic process. 

“Eosinophils can tell us that inflammation is present, but they do not always tell us which disease is driving it,” says Tetsuo Shoda, MD, PhD, corresponding author of the study. “Our goal is not to replace the pathologist, endoscopy or clinical assessment. It is to add molecular information when conventional findings leave uncertainty.” 

Why Diagnosis Can Be Difficult 

EoC is a rare inflammatory condition characterized by increased eosinophils, a type of white blood cell, in the colon. IBD, which includes Crohn disease and ulcerative colitis, can also be associated with elevated eosinophils. In some cases, the two diseases can appear remarkably similar under the microscope. 

That overlap presents an important challenge because EoC and IBD are distinct diseases that may require different treatment approaches. While pathologists evaluate biopsy findings and clinicians consider symptoms, endoscopy and other testing, there are situations in which the diagnosis remains unclear despite these combined results. 

Previous research has shown that EoC and IBD have different underlying molecular signatures. The new study sought to translate those biological differences into a practical diagnostic tool. 

A New Framework 

Researchers analyzed 88 colonic biopsy samples from 74 patients with EoC, Crohn disease, ulcerative colitis or non-disease controls. They developed a 96-gene gene panel tool called the Colonic Eosinophilia Diagnostic Panel (CEDP) that generates two complementary molecular scores. 

The first score measures eosinophilic inflammation: 

  • Distinguished active EoC from non-disease controls 
  • Correlated with peak eosinophil counts 
  • Reflected molecular disease activity in the colon 

The second score focuses on molecular pathways associated with IBD: 

  • Distinguished active IBD from EoC with very high accuracy 
  • Correlated with endoscopic measures of IBD activity 
  • Identified IBD-associated molecular signatures even in patients whose biopsies contained high levels of eosinophils 

Together, the two scores provide what the researchers describe as a two-component molecular framework. Rather than relying only on eosinophil counts, the panel evaluates distinct biological pathways associated with each disease. 

Looking Ahead 

The researchers emphasize that the CEDP is intended to complement, not replace, established clinical, endoscopic and histologic evaluation. The CEDP may offer additional evidence when conventional diagnostic approaches do not provide a clear answer.  

The CEDP remains a research-stage tool and will require prospective validation in larger independent cohorts before clinical implementation. Future studies will also examine whether molecular scores could help monitor disease activity or treatment response over time.  

 About the Study 

The work was led by Richard J. Taylor, MD, during his pediatric gastroenterology fellowship at Cincinnati Children’s. Taylor is now a faculty member at Cincinnati Children’s. Tetsuo Shoda, MD, PhD, served as corresponding author.  

The study also highlights the collaborative research environment surrounding eosinophilic gastrointestinal diseases at Cincinnati Children’s. Taylor led the project as a GI fellow while working with senior faculty across gastroenterology and allergy/immunology, including Lee Denson, MD, Vincent Mukkada, MD, and Marc Rothenberg, MD, PhD. The study also drew on samples and expertise from the national Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). 

Together with the recent EoG proteomics study led by fellow Molly Ahye, MD, this work illustrates how fellows, faculty mentors and multidisciplinary research programs can work together to advance precision approaches for eosinophilic gastrointestinal diseases. 


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Publication Information
Original title: Precision Diagnosis and Differentiation of Eosinophilic Colitis and Inflammatory Bowel Disease Using a Tissue-Based Molecular Gene Expression Panel
Published in: The Journal of Allergy and Clinical Immunology
Publish date: October 28, 2026
Read the findings

Research By

Tetsuo Shoda, MD, PhD
Tetsuo Shoda, MD, PhD
Division of Allergy and Immunology

The Shoda Lab at Cincinnati Children’s is working to identify the key genes and genetic regulatory mechanisms that predispose patients to eosinophilic conditions, especially eosinophilic gastrointestinal diseases (EGID).

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