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This disease can be caused by a food allergy and prevent children from eating. A new study may show how to treat it

Eosiniphilic esophagitis was not identified as a disease until the 1990s. Decades later, a treatment may have been discovered

Date:
July 31, 2023
Source:
Tulane University
Summary:
Eosiniphilic esophagitis occurs more frequently in children and can prevent food from being swallowed, potentially leading to malnutrition, weight loss and poor growth. A new study has identified the pathway that causes the chronic immune system disease and a novel treatment strategy.
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A new study from Tulane University has identified a new treatment for a chronic immune system disease that can prevent children from eating.

Eosinophilic esophagitis (EoE) is triggered by food allergies or airborne allergens which causes a type of white blood cell, eosinophils, to build up in the lining of the esophagus. This causes the esophagus to shorten and the esophageal wall to thicken, making swallowing difficult and causing food to get stuck in the throat.

The disease occurs in an estimated 1 in 2,000 adults but more frequently affects children (1 in 1,500) where symptoms can be harder to diagnose and pose greater risks as difficulty feeding can lead to malnutrition, weight loss and poor growth.

The new study, published in Nature's Communications Biology journal, found that the disease is caused by Interleukin-18 (IL-18), a protein involved in the innate immune response that can cause inflammation if produced in excess. When a food allergen enters the body, it activates a pathway responsible for regulating the innate immune system, resulting in the release of proinflammatory proteins like IL-18. This produces the eosinophils which damage the esophagus.

The study found that successfully inhibiting this pathway, called the NLRP3 pathway, and the release of IL-18 prevented the development of EoE from both food and airborne allergens.

"Parents and doctors may not be aware of this, but this is a very prominent and serious disease in the pediatric population, and it is increasing in number because it is directly related to food allergens, which are also on the rise," said lead author Dr. Anil Mishra, director of the Eosinophilic Disorder Center at the Tulane University School of Medicine. "In this study, we show that after treating the disease in animals, the disease is gone and completely in remission."

The findings are crucial for a disease that was not identified until the 1990s. For many years, EoE was misdiagnosed as gastrointestinal reflux disease (GERD), despite GERD medication being ineffective for treating EoE. Additionally, this study's findings replace decades of thinking that Th2 cells play a major role in triggering EoE.

"Given the paucity of mechanistic information and treatment strategies for EoE, we feel the proposed studies are highly relevant and are poised to have a major impact on establishing the significance of NLRP3-IL-18 pathway in the initiation of EoE pathogenesis," Mishra said.

The study identified one existing drug, VX-765, as an inhibitor that may work as a treatment for humans. Importantly, this inhibitor would only deplete pathogenic eosinophils generated and transformed by IL-18 and not affect white blood cells created by IL-5, a protein important for maintaining innate immunity.

Mishra said a clinical trial would be the next step to determining the treatment's effectiveness.


Story Source:

Materials provided by Tulane University. Note: Content may be edited for style and length.


Journal Reference:

  1. Chandra Sekhar Yadavalli, Sathisha Upparahalli Venkateshaiah, Sandeep Kumar, Hemanth Kumar Kandikattu, Lokanatha Oruganti, Chandra Sekhar Kathera, Anil Mishra. Allergen-induced NLRP3/caspase1/IL-18 signaling initiate eosinophilic esophagitis and respective inhibitors protect disease pathogenesis. Communications Biology, 2023; 6 (1) DOI: 10.1038/s42003-023-05130-4

Cite This Page:

Tulane University. "This disease can be caused by a food allergy and prevent children from eating. A new study may show how to treat it." ScienceDaily. ScienceDaily, 31 July 2023. <www.sciencedaily.com/releases/2023/07/230731110713.htm>.
Tulane University. (2023, July 31). This disease can be caused by a food allergy and prevent children from eating. A new study may show how to treat it. ScienceDaily. Retrieved October 31, 2024 from www.sciencedaily.com/releases/2023/07/230731110713.htm
Tulane University. "This disease can be caused by a food allergy and prevent children from eating. A new study may show how to treat it." ScienceDaily. www.sciencedaily.com/releases/2023/07/230731110713.htm (accessed October 31, 2024).

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