Scientists at Aarhus University have described the structure of an IgE antibody for the very first time.
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In a paper published in the scientific journal Allergy, the team describes how they revealed the structure of this antibody that is responsible for allergic reactions, as well as detailing the mode of action of an anti-allergy therapeutic antibody. These breakthrough findings will likely influence the development of future medicines.
The increasing prevalence of allergic diseases
The immune system relies greatly on the use of antibodies to protect the human body from invading organisms such as pathogenic bacteria and viruses. They are an important line of defense that works to prevent the establishment of illness and disease.
While there are several distinct antibodies, in general, they work by binding to an antigen that is viewed as potentially threatening, as well as by triggering appropriate immune responses. Research has shown that antibodies have a high degree of flexibility to give them maximum efficacy.
Across the globe, allergic diseases impact over a billion people, a figure that is expected to quadruple over the next 30 years. Regions that are rapidly urbanizing are those at particular risk of the increasing prevalence of allergic diseases along with their detrimental socio-economic effects, such as high costs to healthcare systems.
Currently, not all allergies can be treated by available medicines. Scientists at Aarhus University aimed to address this with their research which aimed to open up avenues for new kinds of allergy medicines.
Using EM microscopy to uncover the structure of IgE
IgE antibodies are generated when a person has an allergic reaction to allergens that enter the body. The blood transports these IgE antibodies which are added onto the immune system’s effector cells. These effector cells that are combined with IgE antibodies are triggered when an allergic person is exposed to certain allergens. This initiates the release of high levels of mediators and histamine which results in the body producing an immediate allergic reaction.
The researchers investigated these antibodies using electron microscopy (EM) alongside the method of small-angle x-ray scattering. The results of their findings revealed the three-dimensional structure of IgE antibodies for the first time. They demonstrated that the general rule of flexibility in antibodies does not apply with IgE antibodies.
EM microscopy showed that the structure of the allergen-binding moieties of these antibodies is rigid and well-defined, rather than being flexible, as has been demonstrated in many other well-studied antibody isotypes.
In addition, the findings of the study uncovered the effect of a therapeutic antibody, in terms of structure and function, on the IgE antibody. The therapeutic antibody was found to bind to the IgE antibody, having the impact of preventing allergic reactions.
The team was also able to uncover the structural changes that incur following neutralization of the IgE antibody by the therapeutic antibody. These findings are important in enabling scientists to gain essential insights into how the IgE antibody recognizes allergens as well as how they identify the two kinds of IgE receptors that are located on the cell surface of our body’s immune cells.
Until now, researchers had failed to understand why IgE antibodies seemed to differ from other antibodies. This research has clarified why these differences occur, which should open the door to the development of new therapeutic approaches to allergies.
Developing new allergy treatments
The team was successful in defining the IgE antibody’s structure, which is vital to gaining a deeper understanding of how the body develops allergic responses. Shortly, we could see new and more effective strategies in treating allergies develop from this advancement in knowledge.
First, more studies will need to be conducted to further explore the nature of the IgE molecule, however, it already provides an interesting starting point for the development of future medicines.
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