Researchers have uncovered a new target which could help treat severe allergic diseases. 

In a study published in The Journal of Allergy and Clinical Immunology, a team led by Associate Professor Tomoaki Ando and Professor Jiro Kitaura at Juntendo University Graduate School of Medicine identified Fab (fragment antigen-binding) antibody fragments. These fragments target the immunoglobulin E (IgE) Cε2 domain and disrupt the IgE–FcεRI complex, effectively stripping IgE from mast cells. 

Several severe allergic diseases are driven by IgE bound to immune cells, such as mast cells. Current therapies have delayed effect in these diseases as they can only eliminate free IgE in the serum.  

Researchers have now identified antibody fragments that target Cε2 domain of IgE, capable of destabilising its complex with the receptor FcεRI and removing it from mast cells. The antibody fragments offer a potential rapid-acting therapy for IgE-driven allergic diseases. 

Findings show first evidence of potential therapeutic target

To systematically investigate antibodies against the human IgE Cε2 domain, the researchers generated Fab antibody libraries from immunised rabbits and screened them for activity against pre-formed IgE–FcεRI complexes.  

This approach revealed marked differences among Fab clones in their ability to destabilise IgE–receptor interactions. The most potent Fab fragments efficiently removed IgE already bound to mast cell surface receptors. 

“Previous studies in mice suggested that targeting the Cε2 domain could suppress IgE-dependent mast cell activation, yet whether this strategy could be applied to human IgE remained unclear due to substantial species differences between human and murine IgE,” said Dr Ando. 

“This gap in knowledge prompted us to ask whether the human IgE Cε2 domain could be exploited as a novel therapeutic target to destabilise IgE–receptor interactions.” 

The team further evaluated whether these Fab antibody fragments could suppress IgE-driven allergic reactions in FcεRI-humanised mouse models. Their experiments showed that the most effective Fab clones significantly reduced allergic responses and inflammation in vivo, demonstrating both cellular and physiological efficacy. 

“The study demonstrates, for the first time, that the Cε2 domain of human IgE is a viable therapeutic target, and identifies multiple antibody fragments that show rapid efficacy in cellular assays and in vivo anaphylaxis models,” Dr Ando added. 

“The most immediate real-world application of our findings is the development of a next-generation antibody therapy for allergic diseases that require rapid and reliable symptom control.  

“In addition, this strategy could be applied in clinical settings where temporary but rapid desensitisation is needed, such as before allergen exposure during immunotherapy or medical procedures.”