Innovations in Allergy Immunotherapy: Perspectives From Sarita Patil, MD

Food allergies represent a growing public health concern, affecting millions of individuals globally and posing significant clinical and quality-of-life challenges. Current treatments, including allergen immunotherapy, offer hope for managing allergic responses; however, their efficacy remains inconsistent, with only a subset of patients achieving long-term tolerance. This underscores the critical need for innovative research to advance our understanding of immunological mechanisms and to improve therapeutic strategies.

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Sarita Patil, MD, principal investigator at the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital, brings a unique perspective to this challenge, integrating clinical expertise with groundbreaking laboratory research. As an Assistant Physician at Massachusetts General Hospital and Assistant Professor of Medicine at Harvard Medical School, Dr. Patil investigates the role of allergen-specific antibodies in achieving clinical tolerance, aiming to transform the landscape of food allergy management.

Q: What inspired your research focus on food allergies?

Dr. Patil: I was inspired by both my personal curiosity about how immunotherapy works, not only in food allergies but also other allergies, and my lifelong love of understanding how antibodies work in the body. Our practice of medicine has been completely revolutionized by our ability to harness these tiny but powerful molecules. I've been inspired by both the science and clinical medicine behind those revolutions and believe that we can understand antibodies, both those that cause disease and those that treat disease to develop better therapies and ways of treating allergies.

Q: How is modern society affecting the development of food allergies?

Dr. Patil: Recent work identifying that early introduction of food allergens significantly reduces the frequency of food allergies highlights the importance of orally exposing infants early and often to allergenic foods. Our modern practices around parenting can make these preventive measures especially challenging to implement. Overcoming these challenges, as well as the challenges around balancing safety and preventive measures is very important to the health of the next generation. As a society, we need to come together and support both child health and parenting to support the next generation.

Q: What is induced tolerance to allergens? How does your work seek to develop therapies using allergen tolerance?

Dr. Patil: Allergies develop when the human body has a harmful response to an otherwise harmless allergen. In treatment for allergies, we seek to combat that hypersensitivity. Allergen immunotherapy is an effective way of increasing exposure to allergens to change the body's response to that allergen immunologically. However, only a few people have durable changes, or tolerance. We sought to understand why that occurs during peanut oral immunotherapy so we can figure out how to make the therapy more effective for more people. During immunotherapy, people who have the IgE allergy antibodies to food allergens also make another type of protective antibody, IgG4 antibodies. We sought to understand whether some of these antibodies were important to long-term tolerance.

Q: Can you highlight some of the immunological mechanisms your work seeks to identify?

Dr. Patil: We found that antibodies that can bind to peanut allergens on certain areas are really good at preventing those allergen antibodies from being able to be activated by allergens. We called these IgG4 antibodies neutralizing antibodies since they literally neutralize the allergen by preventing IgE-mediated allergic reactions.

Q: What methods or techniques does your lab use to identify food allergy biomarkers?

Dr. Patil: We use many methods. About a decade ago, we pioneered a technique using allergen multimers to identify those cells that make allergen-specific antibodies. That tool, combined with our ability to use single-cell cloning, where we could then artificially make the antibody that the B cells were producing in the person's body, really gave us important tools to be able to identify the way that protective antibodies work. We were able to use structural biology techniques, like X-ray crystallography and biolayer interferometry, where we can look at how the antibody and allergens interact. Now, with advanced tools, including artificial intelligence-based tools, we can further advance this knowledge.

Q: How do you envision using omics technologies (e.g., transcriptomics, metabolomics) to advance our understanding and management of food allergies?

Dr. Patil: We have been using transcriptomics, first starting just on an antibody level, and now on the level of the whole transcriptome, to dissect how antibody responses in the body work. We can now use multi-dimensional information from the allergen-specific B cells to combine information about the antibody that these cells make and information about the B cell and its abilities to be able to comprehensively understand the dynamics of antibody development. By comparing these aspects during immunotherapy, we will be able to better translate our understanding of protective antibodies into effective therapies.

Q: What are the practical implications of your findings for clinicians managing patients with food allergies?

Dr. Patil: Our work has led to development of biomarker assays that let us look for those specific neutralizing antibodies in durable tolerance. Previously, in the clinical trials of immunotherapy, the only way to figure out if someone had long-lasting tolerance was to stop therapy and then challenge the patient, which is time-consuming, laborious, and risks allergic reactions. A biomarker assay using a blood sample that can assess long-term tolerance without the need for an oral challenge would be immensely useful. We sought to develop an assay that can identify neutralizing IgG4 antibodies in the blood of patients undergoing immunotherapy and found that these antibodies are only increased in people after immunotherapy who have long-term tolerance. This assay could be very useful in not only identifying the effectiveness of immunotherapy but also in how we counsel our patients around these therapies. Our goal with all of our work is to improve the lives of people affected by food allergies, and we hope this work will pave the way for the future.

Dr. Patil's research underscores the transformative potential of immunological advancements in the management of food allergies. By identifying protective antibodies and leveraging innovative techniques such as allergen multimers, structural biology, and transcriptomics, her work bridges the gap between bench research and clinical practice. The development of blood-based biomarker assays to assess long-term tolerance not only enhances therapeutic precision but also minimizes the risks associated with traditional oral food challenges. As her findings inspire new therapeutic strategies and inform future clinical trials, they pave the way for safer, more effective treatments, offering hope to millions affected by food allergies.

Learn more about the Center for Immunology & Inflammatory Diseases

Learn more about the Patil laboratory and research