Save the Date
FASI Annual Symposium
June 3, 2022
ADVANCES IN MUCOSAL IMMUNITY
Please join us at our next annual symposium to discuss innovative advancements in mucosal immunity. We’ll be gathering in person at the Broad Institute and virtually via Zoom.
To register, click here.
$6890741 FASI awarded a total of $6,890,741 in grants and gifts
11 Different research institutions
Game Changing Discoveries
Chief, Pediatric Allergy & Immunology
Massachusetts General Hospital
Wayne Shreffler, MD, Ph.D., is a physician-scientist who treats patients with allergic disorders. When Dr. Shreffler isn’t in the clinic, he is pioneering research in food allergies, including eosinophilic esophagitis. EoE is a chronic disease caused by inflammation in the esophagus. It can lead to daily problems like difficulty swallowing, pain, scarring and narrowing of the tube.
What causes EoE to develop is still unknown. However, chronic inflammation is often driven by exposure to specific food allergens – usually dairy, eggs and wheat. Identifying those specific allergens is a burdensome process involving cycles of elimination diets followed by a procedure to sample tissue from the esophagus. Due to this burden, patients will manage with chronic medications instead (though it’s not always successful).
Dr. Shreffler and his colleagues – including FASI scientists Dr. Christopher Love, Ph.D., and Dr. Qian Yuan, MD – are hoping to change the way EoE is diagnosed and treated. The team recently published a landmark paper in the journal Science Immunology that implicates specific pathways allergen immune cells may use to find their way to the esophagus. This discovery has potential to become a new form of treatment. And because the cells can be detected in blood, it also opens up the potential to dramatically reduce the need for repeated endoscopies.
We asked Dr. Shreffler what his new findings mean for people living with EoE.
EoE is an allergic condition characterized by chronic, often painful inflammation of the esophagus. It affects more than 180,000 people in the US. We know that EoE can be triggered by exposure to specific foods. It is also a common side effect of the oral immunotherapy (OIT) treatment of patients with immediate food allergies, affecting about 1 in 20 patients who try OIT. Unfortunately, the treatment options aren’t that great — the best approaches are food avoidance and/or steroid treatment to dampen the immune response.
A big challenge is that regular endoscopies and biopsies are essential for diagnosing and monitoring the disease. These are relatively invasive and require a trip to the operating suite. And once diagnosed, it doesn’t solve the problem as treatment options are limited. For patients that wish to treat by allergen avoidance rather than chronic medications, this is a repeated process of trial and error. Understanding the biology of what drives the immune system to attack the esophagus is a critical question that we seek to understand.
This study would not have been possible even five years ago. Recently, Dr. Chris Love and colleagues at MIT developed a platform for high-throughput single-cell RNA sequencing that is particularly well suited to studying EoE. This technology allowed us to sample tissue from the esophagus and blood and identify the immune cells causing the inflammation. This led our team to discover a role for a molecule called GPR15, expressed on a very specific allergy inflammation driving subset of T-cells, which they use to travel to the esophagus and cause inflammation.
What was also exciting to find is that this rare subset of GPR15+ cells is detectable in the blood. We found that these GPR15+ cells in both the blood and esophagus in some cases shared the same T cell receptor – the feature that determines whether a T cell recognizes a milk allergen, or an egg allergen, or something entirely different. We can rapidly exploit this information to develop new non-invasive ways to diagnose and manage patients, and in the future it may help us identify the allergen that is driving disease – currently the only way to do this is to monitor patients as they adhere to strict avoidance diets until the specific allergen is identified.
Finally, our team has separately identified GPR15 expression as a predictor of poor responses to oral immunotherapy (OIT) in food allergy. Currently, there is no way to determine if one food allergic patient will tolerate OIT. This would help us identify which patients are good candidates.
Our findings represent a significant step forward in understanding the biology behind EoE. This is the sort of research that FASI is uniquely situated to support. We are expanding the scope of our initial study to evaluate a larger population. We’re now recruiting additional patients and securing funding to propel the next wave of discoveries. This study is a perfect example of why partnering with multiple collaborators from different scientific disciplines can drive innovation, making discoveries faster.