Allergies are a global health concern, impacting countless individuals and placing a significant burden on healthcare systems. Severe allergic reactions, such as anaphylaxis, asthma, food allergies, and allergic rhinitis, are triggered by immunoglobulin E (IgE), an antibody that binds to immune cells like mast cells and basophils. When IgE remains attached, it leads to exaggerated immune responses to allergens, causing discomfort and potential health risks. While current anti-allergy treatments can neutralize free IgE in the bloodstream, they fall short in efficiently removing IgE bound to immune cells, resulting in delayed symptom relief.
In a groundbreaking study published in The Journal of Allergy and Clinical Immunology on December 11, 2025, researchers from Juntendo University Graduate School of Medicine, led by Associate Professor Tomoaki Ando and Professor Jiro Kitaura, in collaboration with Toshiaki Maruyama of Abwiz Bio Inc., have identified a potential game-changer. They've discovered Fab (fragment antigen-binding) antibody fragments that target a unique domain in IgE, known as Cε2, and disrupt the IgE-FcεRI complex, effectively removing IgE from mast cells.
Dr. Ando explains, "Previous studies in mice hinted at the potential of targeting the Cε2 domain to suppress IgE-dependent mast cell activation. However, due to significant differences between human and murine IgE, it remained uncertain if this approach would work for humans. This knowledge gap motivated us to explore whether the human IgE Cε2 domain could be a novel therapeutic target to disrupt IgE-receptor interactions."
To systematically investigate antibodies against the human IgE Cε2 domain, the researchers created Fab antibody libraries from immunized rabbits and screened them for activity against pre-formed IgE-FcεRI complexes. This meticulous approach revealed notable variations among Fab clones in their ability to disrupt IgE-receptor interactions. The most potent Fab fragments demonstrated an impressive efficiency in removing IgE already bound to mast cell surface receptors.
The team took their research further by evaluating the potential of these Fab antibody fragments to suppress IgE-driven allergic reactions in FcεRI-humanized mouse models. Their experiments showed that the most effective Fab clones significantly reduced allergic responses and inflammation in vivo, showcasing both cellular and physiological efficacy.
Dr. Ando highlights, "Our study provides the first evidence that the Cε2 domain of human IgE is a viable therapeutic target. We've identified multiple antibody fragments that exhibit rapid efficacy in cellular assays and in vivo anaphylaxis models. This discovery opens up exciting possibilities for the development of a next-generation antibody therapy for allergic diseases, offering rapid and reliable symptom control. Additionally, this strategy could be invaluable in clinical scenarios where temporary but swift desensitization is crucial, such as before allergen exposure during immunotherapy or medical procedures."
IgE circulates at low levels in human serum, making it susceptible to efficient neutralization by existing therapies. However, their inability to remove IgE bound to mast cells has been a persistent challenge in achieving rapid symptom control. Antibody-based strategies targeting the human Cε2 domain offer a promising solution by directly destabilizing IgE-receptor complexes. While further studies are needed to confirm their clinical safety and efficacy, this research paves the way for innovative allergy treatments.
References:
Wang, H., Ando, T., Maruyama, T., Okumura, S. C. J., Izawa, K., Kaitani, A., ... & Kitaura, J. (2025). Fabs targeting a Cε2 epitope disassemble IgE-receptor complexes and suppress anaphylaxis. The Journal of Allergy and Clinical Immunology, 10.1016/j.jaci.2025.11.010.
About the Researchers:
Associate Professor Tomoaki Ando, MD, PhD, is an esteemed researcher at the Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo, Japan. His expertise spans pediatrics, allergology, and immunology, with a focus on understanding the cellular and molecular mechanisms underlying allergic diseases. Dr. Ando's research delves into mast cell biology, IgE-mediated allergic responses, allergen cross-reactivity, and inflammatory pathways, aiming to translate immunological insights into cutting-edge therapeutic strategies for allergic and inflammatory disorders.
