McMaster team finds blocking key pathway can prevent anaphylaxis

New research by AllerGen investigators Drs. Manel Jordana and Susan Waserman and their team at McMaster University has demonstrated that blocking a key pathway involved in the allergic response can fully protect against anaphylaxis.

The article was published online in the Journal of Allergy and Clinical Immunology and is featured as an Editor’s Choice in its April 2021 issue.

“Our findings point to a promising, potentially transformative treatment for peanut and likely other food allergies,” says Dr. Jordana, a Professor of Medicine at McMaster.

Register here for a webinar with Dr. Jordana on this research and its implications for the future treatment of food allergies, taking place on 4 May 2021 from 12:00 to 1:00 pm EDT.

The Jordana-Waserman lab has been studying why allergies to some foods, such as peanut, often persist for a lifetime. In food allergy, the immune system mistakenly identifies a specific food protein as harmful and triggers the production of an antibody called IgE to eliminate it.

Their previous AllerGen-supported research found that specialized cells “remember” the food allergen they are specific for, and upon re-encountering the allergen, these long-lived “memory cells” become activated and replenish the short-lived cells that produce IgE, which ultimately triggers the allergic reaction.

The team has been working to understand the biological mechanisms underlying that “replenishment.”

The main proteins or signalling molecules involved in triggering IgE production are interleukin 4 (IL-4) and interleukin 13 (IL-13). In the new study, the team found that blocking signalling by IL-4 and IL-13 in humans or mice with established peanut allergy completely inhibited the production of IgE in a human model and fully prevented anaphylaxis in a mouse model.

“We already knew that IL-4/IL-13 signalling is central to the initiation of food allergy,” explains Kelly Bruton, a PhD candidate who led the project along with Paul Spill. “In the current study, we have shown that using an IL-4 receptor alpha blocking antibody, we can interrupt the reactivation of the immunologic memory to divert the allergic response and ultimately prevent anaphylaxis.”

The study was conducted using blood cells from human volunteers with peanut allergy, as well as a murine (mouse) model that mimics key features of human food allergy.

“A most interesting finding is that in mice with allergy, the IL-4 receptor blockade provided long-lasting suppression of the IgE recall response even after clearance of the blocking antibody and fully protected against anaphylaxis,” says Bruton. “These results spotlight IL-4 receptor blockade as a therapy with disease-transformative potential for the treatment of food allergy and offers new hope for our patients,” comments Dr. Waserman.

The research team that conducted this study involved several former AllerGen Highly Qualified Personnel, including co-first authors Kelly Bruton and Paul Spill, Saba Manzoor, Joshua Koenig, Yosef Ellenbogen, and Dr. Rodrigo Jiménez-Saiz.