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Dr Stephanie Trezise – Massachusetts General Hospital & Harvard Medical School

20/02/2024 2:00 pm - 20/02/2024 3:00 pm
Location
Davis Auditorium

WEHI Special Immunology Seminar hosted by Professor Stephen Nutt & Dr Simon Willis
 

Dr Stephanie Trezise
Postdoctoral fellow – Anthony Laboratory, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School; Affiliate Postdoc – Broad Institute

 

A protective role for IgG2 in food allergy

 

Davis Auditorium

Join via TEAMS

Including Q&A session

 

 

Peanut allergy is one of the most common food allergies in western countries, affecting approximately 2% of the general population. The primary treatment for allergic individuals is peanut avoidance, however, accidental exposure is common and can result in life-threatening anaphylaxis. Peanut oral immunotherapy (OIT), which involves feeding incrementally increasing doses of peanut to allergic individuals to induce tolerance has shown some promise, with a subset of patients developing a sustained unresponsiveness to peanuts following this therapy. However, the success rate of this therapy remains low, with the majority of patients remaining sensitive to peanuts, or only developing a transient desensitization which is lost once OIT is stopped. The current model is that sustained unresponsiveness derives from increased peanut-specific IgG4, which protects from anaphylaxis by masking IgE epitopes and binding to the inhibitory Fcγ receptor, FcγRIIB, on the surface of mast cells and basophils to prevent degranulation. However, peanut-specific IgG4 increases in all individuals undergoing OIT, so IgG4 titer alone is not sufficient to explain this protection.

 

Using an unbiased mass spectrometry approach to interrogate changes in peanut-reactive IgG responses in patients undergoing peanut OIT, we identified a signature that associates with the development of sustained unresponsiveness. We used an in vivo food anaphylaxis model to identify which elements of this signature provide protection. This approach revealed a surprising role for both allergen-specific IgG2 and the engagement of activating Fcγ receptors following oral allergen challenge.

 

Stephanie is currently a postdoctoral fellow in the Anthony laboratory in the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital and Harvard Medical School, and an affiliate postdoc of the Broad Institute. She previously completed her PhD with Professor Stephen Nutt at the Walter and Eliza Hall Institute where she used CRISPR screening approaches to identify novel regulators of antibody secreting cell biology. Since beginning her postdoctoral position, Stephanie has continued to focus on understanding how antibody responses are regulated, and how changes in these responses can impact human health in the contexts of allergy, inflammatory disease and following vaccination.

 

All welcome!

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