Israeli scientists identify protein that could prevent painful food allergy disease

The disease - an inflammation of the oesophagus - affects an estimated 1 in 2,500 individuals. Flare-ups are caused by an abnormal allergic reaction to certain foods or environmental triggers that lead to inflammation and tissue changes in the oesophagus. Left untreated, scarring narrows the width of the oesophagus, making it difficult and painful to swallow food. In extreme cases, the oesophagus can even tear.

There is no cure, and it is managed primarily by diet and medicine.

But scientists at Tel Aviv University identified a protein whose neutralisation may prevent the onset of EoE.

The study, conducted at the university's Gray Faculty of Medical and Health Sciences, focused on the protein thymic stromal lymphopoietin (TSLP). Researchers found that blocking it in experimental models either prevented the disease entirely or dramatically reduced its severity. Their findings were published in Allergy, a peer-reviewed journal.

"Eosinophilic Esophagitis, or EoE, is a type of food allergy. It is a chronic inflammation of the esophagus caused by an abnormal immune response to food -- mainly milk, eggs, wheat, nuts, fish, and more," said Prof. Ariel Munitz, who led the study alongside doctoral student Anish Dsilva. "The disease is characterized by an accumulation of eosinophils, a type of white blood cell that is not typically present in a healthy esophagus."

Symptoms include difficulty swallowing, chest and abdominal pain, food getting stuck in the throat, and in children, growth delays. EoE is often linked to asthma and atopic dermatitis. Current treatments involve strict elimination diets or amino acid-based formulas, with limited effectiveness.

"Over the past decade, there has been a concerning rise in the prevalence of EoE worldwide, including in Israel," Munitz said. "We are studying the disease in depth to understand the involvement of various immune system components in its progression. These components may serve as targets for future treatment for this disease, and for other allergic disorders as well."

A previous study from Munitz's lab developed an experimental model replicating EoE symptoms in humans. Building on that work, the team focused on epithelial cells -- the protective outer layer lining the esophagus. "In allergic conditions, epithelial cells release various substances in response to encountering an allergen, and these substances trigger the chain of events that initiate the inflammatory process we experience as an allergy attack," Munitz explained.

The researchers observed that epithelial cells in their EoE model secreted high levels of two proteins: IL-33 and TSLP. They also found immune cells in esophageal tissue with receptors for both proteins, suggesting that each could play a role in disease development. To pinpoint which protein was more influential, the team used genetic engineering to create models lacking one protein at a time.

The results were striking: removing IL-33 had little effect, but removing TSLP led to marked improvement -- in many cases, the disease did not develop at all. Antibody treatments designed to neutralize TSLP produced similar results, with significant reductions in symptoms. Further genetic and bioinformatic analysis confirmed that TSLP acts as a "key regulator" of the disease process.

"These findings suggest that TSLP is not just involved but is central to driving EoE," Munitz said. "We know that pharmaceutical companies are currently developing a variety of antibodies targeting disease-causing proteins, under the broad category of biological therapies, including antibodies against TSLP. We believe these antibodies could serve as an effective treatment for EoE."

The research was carried out in collaboration with Dr. Chen Varol of Ichilov Hospital, Prof. Marc Rothenberg of Cincinnati Children's Hospital, and the AstraZeneca pharmaceutical company.

If future clinical trials confirm the findings, neutralizing TSLP could offer a targeted, less burdensome treatment for patients, potentially preventing years of discomfort and dietary restrictions.

"EoE causes significant suffering and is becoming increasingly prevalent worldwide," Munitz said. "Our study offers real hope for a therapy that addresses the disease at its source." (ANI/ TPS)