A new study, published online Sept. 12, 2023, in Science Signaling, offers a ground-breaking perspective on the role of Thymic Stromal Lymphopoietin (TSLP) in eosinophilic oesophagitis (EoE), presenting the potential for both a non-invasive blood test and targeted monoclonal antibody treatments.

Introduction

The study was led by Yrina Rochman, PhD, and Marc Rothenberg, MD, PhD, who serves as the Division of Allergy and Immunology director. Other contributors from Cincinnati Children’s include Artem Barski, PhD, Michael Kotliar, MS, Netali Ben-Baruch Morgenstern, PhD, and Ting Wen, PhD.

Understanding TSLP

TSLP (Thymic stromal lymphopoietin) is a cytokine recognised for its ability to induce Type 2 immune responses. It acts mainly by initiating the development of memory T cells, which are then ready to attack pathogenic cells. 

Interest in blocking the influence of TSLP in various diseases has recently intensified. For example, in 2021, the FDA approved tezepelumab, a monoclonal antibody, as an adjunct treatment for severe, uncontrolled asthma.

TSLP’s Direct Influence on EoE

In contrast to studies relying on mouse models, this investigation employed tissue samples from individuals diagnosed with EoE. The researchers noted a higher count of cells expressing the TSLP receptor in these samples compared to those from healthy controls. Moreover, TSLP demonstrated the ability to augment the number of its receptor cells, intensifying the inflammatory process.

The Genetic Impact

The team analysed how TSLP altered the expression of 212 genes and observed a significant enrichment of the transcription factors BATF and IRF4. This led to a “feed-forward loop” that triggered a series of reactions contributing to allergic inflammation. 

The number of T cells influenced by TSLP correlated with the eosinophil count in the biopsy samples.

What This Means For People With Eosinophilic-Associated Diseases (EADs)

“In light of these results and the high clinical cost of anti-TSLP biologics, our study expands the rationale for a noninvasive screening test before treatment, aiming to offer anti-TSLP treatment especially to patients with memory CD4+ T cells that exhibit high responsiveness to TSLP. It also is possible that our findings can be extended to other allergic disorders that involve a high frequency of TSLP-responsive cells.”

Marc Rothenberg, MD, PhD, director of the Division of Allergy and Immunology, Cincinnati Centre for Eosinophilic Disorders

Many of our community members have navigated a challenging journey to find the correct diagnosis and treatment.  Without effective non-invasive diagnostic tools, their medical journeys often led to trial-and-error approaches before reaching the necessary invasive procedures like biopsies to confirm a diagnosis.

New hope for a diagnostic blood test

The research on TSLP potentially enables a non-invasive blood test for the early identification of eosinophilic diseases. 

Identifying TSLP sensitivity before treatment starts may eliminate the guesswork, sparing patients from undergoing costly and ineffective treatments. 

The tailored treatment could offer more effective symptom relief and perhaps even lead to long-term remission, ultimately uplifting the patient’s quality of life.

In addition, these findings on TSLP may not be limited to EoE. They could also offer new pathways for treatment in other eosinophilic or allergic conditions, which are common among people with EADs. 

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