The general structure of the antibody type IgE, which is the essential molecule in allergy disorders, has been described by an international research team. This is a significant scientific accomplishment that sheds light on the basic mechanics of allergic reactions and could pave the way for more efficient allergy treatment.
The new findings were recently published in the scholarly journal Allergy. Antibodies are important and diverse molecules in the immune system of humans. Antibodies in humans have a number of common characteristics, including the ability to bind to potentially dangerous antigens and the ability to trigger correct immunological responses.
Antibodies are adaptable in order to maximize their efficacy, according to one of the immunobiology’s cornerstones. For their investigation, a group of researchers from Aarhus, Denmark, and Marburg, Germany, used EM microscopy and small-angle x-ray scattering.
Scientist Michaela Miehe and Postdoc Rasmus K Jensen of Aarhus University collaborated closely during the past two years to accomplish the results. The study team can now explain the three-dimensional structure of IgE based on their findings. The scientists participating were taken aback by the results they obtained.
“For the first time, we could show that IgE antibodies are unique and are violating the dogma of antibody flexibility. My work with electron microscopy demonstrated directly that IgE is a highly rigid molecule with a defined architecture of the allergen-binding moieties, which is different from the behavior of the other antibody isotypes we know,” explains Postdoc Rasmus K Jensen.
The researchers also looked at the structural and functional effects on the IgE molecule of a therapeutic antibody that is now being investigated in clinical trials. This therapeutic antibody, which is not the same as IgE, binds to IgE and protects against allergic responses.
“Our new results describe the structural changes that IgE undergoes when neutralized by this anti-IgE antibody. This also allows us to understand better, how IgE recognizes allergens and the two IgE receptors sitting on the surface of the immune cells we have in our body,” explains Associate Professor Edzard Spillner.
For the first time, we could show that IgE antibodies are unique and are violating the dogma of antibody flexibility. My work with electron microscopy demonstrated directly that IgE is a highly rigid molecule with a defined architecture of the allergen-binding moieties, which is different from the behavior of the other antibody isotypes we know.
Rasmus K Jensen
Antibody features revised
When exposed to external allergens, an allergic individual creates large levels of IgE molecules that are directed against them. These IgE antibodies circulate in the bloodstream and are loaded onto immune system effector cells.
When these armed cells containing IgE are exposed to allergens, they are stimulated to produce significant amounts of mediators and histamine, resulting in an acute allergic reaction in the body.
“We now realise that the picture we and other researchers have puzzled together through decades by studying IgE fragments differs compared to the new results obtained with intact IgE. It was also most satisfying that we could visualize how the anti-IgE antibody changes the IgE architecture including the antigen binding arms,” explains Professor Gregers Rom Andersen.
The researchers used a variety of recombinant IgE molecules that they created in the lab to conduct their trials. These IgE molecules identify sugar groups found on allergens as well as a home dust mite allergen. The approach, on the other hand, can be applied to almost any form of IgE molecule.
Hope for better medicine
Allergic disorders affect more than one billion people globally, and their frequency is anticipated to rise to four billion by 2050. As a result of environmental and lifestyle changes, the prevalence of allergy disorders and their socioeconomic impact is on the rise in urbanizing regions and the globalizing world.
Aside from the personal anguish of patients, allergic illnesses impose a significant financial burden on health-care systems. Although present medications are unable to control all types of allergies, the researchers are hopeful that their findings may pave the way for the creation of novel allergy medicines.
“We now understand much better and in much more detail the IgE molecule that we want to control and the way it behaves upon treatment of patients with allergy medicine. This also allows us to envision new strategies for developing medicine of the future,” says Edzard Spillner.
While the knowledge gained will ultimately benefit the specific patient, the team will also contribute to the field’s ongoing study.
“The extraordinary characteristics of IgE makes it an exciting object for more detailed studies in concert with molecules within and outside the allergic immune response,” says Gregers Rom Andersen.
Overall, the team’s findings give essential basic and translational knowledge and serve as a springboard for future research, which may be why the Novo Nordisk Foundation backed the study.
