Why natural allergen-specific antibodies cannot always protect against allergies

Newswise — Immunologists found the difference between antibodies that react to birch pollen allergens in healthy people and patients with allergies. The authors also found out why not all classes of antibodies can protect against allergies. The results were published in Allergy. The study was carried out by the research team of the National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia, RUDN University, and the Medical University of Vienna. 

If the immune system perceives a harmless substance as foreign, an allergic reaction occurs. A third of the world’s population suffers from some form of allergy. It means that patient has in their blood specific “key” antibodies that match specific epitopes, the “passwords” for certain allergens. The “password” to which antibodies react is a part of the allergen molecule called an epitope. They can be simple in shape (linear) or twisted into complex shapes (conformational) molecular structures. To treat allergies, scientists study antibodies and their interactions with epitopes. Immunologists from an international research team studied the differences in the molecular structure of epitopes and antibodies of patients without allergies and with allergies to birch pollen.

“It is important to understand whether there are differences between the epitopes that antibodies recognize in patients with and without allergies. It raises some fundamental questions: for example, can natural antibodies protect against allergic reactions when transmitted from mother to child? Or is it possible to use antibodies from healthy people to treat allergies through passive immunization?” comments Evgeniy Smolnikov, senior lecturer at the Department of Immunology of the RUDN University, researcher at the Department of Allergology and Skin Immunopathology of the National Research Center Institute of Immunology Federal Medical-Biological Agency of Russia.

Scientists examined the blood sera of patients with birch pollen allergies and people without allergies. The authors analyzed the specific interaction of IgE antibodies and allotypes of IgG antibodies with various molecular modifications of the main birch pollen allergen Bet v 1. Then authors conducted a laboratory experiment – they took antibodies from people without allergies and tested their ability to block the binding of antibodies from allergy sufferers to Bet v 1. The scientists also investigated whether antibodies from both groups of patients could influence the activation of basophils, a type of white blood cell involved in the development of allergic reactions, by Bet v 1.

IgE antibodies of patients with allergies reacted only to conformational epitopes, and the remaining antibodies (for people from both groups) reacted mainly to linear ones. The conformational epitopes of Bet v 1 turned out to be “masked” – hidden under proteins and available only after the destruction of proteins. Natural antibodies obtained from healthy people were not able to significantly suppress the binding of IgE and Bet v 1 and even increased the activation of basophils. Therefore, they will not be able to protect against allergies.

“IgE and IgG antibodies in patients with and without birch allergy recognize different epitopes of the major birch pollen allergen Bet v 1. That explains why natural IgG does not protect against allergy symptoms. Probably, IgE and IgG for this allergen have different origins,” said Evgeniy Smolnikov, senior lecturer at the Department of Immunology of the RUDN University, researcher at the Department of Allergology and Skin Immunopathology of the State Scientific Center Institute of Immunology of the Federal Medical and Biological Agency of Russia.