Treatment for Chronic Immune System Disease Identified

Tulane University researchers have discovered a novel cure for a chronic immune system condition that prevents youngsters from eating.
Eosinophilic esophagitis (EoE) is caused by food allergies or airborne allergens, which cause eosinophils, a kind of white blood cell, to accumulate in the lining of the esophagus. This shortens the esophagus and thickens the esophageal wall, making swallowing harder and causing food to become lodged in the throat.

The disorder affects around one in every 2,000 adults, but it is more common in children (one in every 1,500), when symptoms can be more difficult to identify and offer greater concerns, as trouble feeding can lead to malnutrition, weight loss, and poor growth.

The current study, published in Nature Communications Biology, discovered that the condition is caused by Interleukin-18 (IL-18), a protein involved in the innate immune response that, when produced in excess, can induce inflammation. When a food allergen enters the body, it activates a pathway that regulates the innate immune system, causing the release of proinflammatory proteins such as IL-18. This results in the production of eosinophils, which cause esophageal injury.

The study discovered that suppressing this route, known as the NLRP3 pathway, and the production of IL-18 successfully reduced 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 discoveries are critical for a condition that was not discovered until the 1990s. EoE was misdiagnosed as gastrointestinal reflux disease (GERD) for many years, despite the fact that GERD treatment proved unsuccessful in treating EoE. Furthermore, the findings of this study refute decades of belief that Th2 cells play a significant role in the onset of 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 investigation identified one existing medicine, VX-765, as an inhibitor that could be used as a human treatment. Importantly, this inhibitor would only reduce pathogenic eosinophils generated and converted by IL-18 and would not effect white blood cells produced by IL-5, a protein necessary for innate defense maintenance.

Mishra stated that the next stage in determining the treatment’s efficacy would be a clinical trial.

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