Diversity of Human Allergen-Specific IgE and Defining Epitope Recognition of Allergic Subjects that are to Undergo Allergen-Specific Immunotherapy

Abstract

Grass pollen allergies caused by Timothy grass affect the lives of many people and have a huge economic impact on our society. Hypersensitivity reactions are triggered by allergens and allergen-specific IgE, leading to degranulation of mast cells releasing bioactive compounds causing allergic symptoms. Improvement of allergen-specific immunotherapy (AIT) involving gradual exposure to the allergen inducing desensitization is crucial for providing an effective cure for allergies, reducing potential side effects, and decreasing the socioeconomic burden. Identifying IgE epitopes on Timothy allergens is crucial for understanding allergy development. This study focuses on IgE responses to Timothy grass allergens Phl p 1, Phl p 2, Phl p 4, Phl p 5 and Phl p 11 in 67 allergic subjects that are to undergo AIT. Furthermore, interactions between IgE and allergens are studied through an epitope mapping assay. Phl p 1 and Phl p 5 were found to be major grass allergens with detected IgE responses of 75% respectively 60%. These findings align with previous research and emphasizes the importance of these major grass allergens in development of allergic disease as well as further development of AIT. Epitope mapping assay for Phl p 2 and Phl p 5 indicates that there is a diverse epitope recognition between subjects confirming personalized patterns of epitope recognition while a low epitope recognition diversity was found for Phl p 11. To fully understand how IgE recognizes epitopes in allergens from pollen, it is necessary to create an antibody panel that binds to epitopes different from those targeted by the monoclonal antibodies used in this research. The next phase of this study would be to analyze sequences to identify overlapping IgE and IgG clones that can serve as biomarkers to evaluate AIT effectiveness. Further characterization of IgE germline repertoire for major grass allergens is necessary for studies of mechanisms of allergies and AIT.

Popular Abstract

The Roles of Antibodies in Pollen Allergy and Improvement of Treatment

Pollen allergies affect about 40% of the European population and these people deserve more efficient treatment options to put an end to their suffering. This can be achieved with more knowledge about disease development and more advanced vaccinations.

The immune system is the body’s defense system protecting us from infections. This is done with help from antibodies which are molecules searching for foreign substances in our body. Sometimes antibodies attack a harmless substance causing an allergic reaction. In this study the focus lies on allergies caused by pollen, which is an allergen from Timothy grass. Pollen from Timothy grass consists of different proteins that can enter the body through airways and cause allergic reactions. Pollen allergy is not only a big problem for affected people as it also has an economic impact on society. Since pollen allergies are very common in Europe affecting about 40% of the population, there is a need to develop more effective treatment therapies that will cure people with allergies.

Allergen-specific immunotherapy, a treatment involving allergy shots or tablets, exposes patients to tiny amounts of allergens gradually increasing the dosage over years. These contain just enough to stimulate the immune system without provoking a full allergic reaction, leading to a cure. Protective antibodies are then produced in our bodies that bind to responsible allergens. By blocking these binding sites, protective antibodies prevent allergy-antibodies from binding to allergens, decreasing the overreaction of immune system. To optimize this method, understanding the location of the sites where both protective and allergy-antibodies bind to allergens is required. Additionally, identifying the most important allergens, those to which most people are allergic to, can improve treatment by making the allergy shots contain only the relevant proteins.

In this study, we have found the two most important allergens that trigger allergies in about 70% of allergic participants. We must now explore whether these allergens could serve as targeted therapy for individuals reactive to them. These exciting findings bring us closer to personalized treatments offering relief to many allergy sufferers. This study also investigated whether the subjects in the study had antibodies that bind the allergen similarly and also if they bind the same site on the allergen as an protective antibody. Findings indicate that for certain allergens the allergy-antibodies from subjects showed varying binding patterns while for other allergens the allergy-antibodies bound in a similar manner. This gives an insight into how protective antibodies could act as a blocking agent after vaccination.

To summarize, this study investigated major allergens from Timothy grass pollen and analyzed how antibodies from different allergic patients interact with these allergens. This is a very important part of development of better and more efficient treatment options for people suffering from pollen allergies.

• author: Malzagova, Anja and Hallberg, Linnea
• supervisor: Mats Ohlin
• organization: Department of Immunotechnology
• course: KIMM05 20241
• year: 2024
• type: H2 - Master's Degree (Two Years)
• subject: Biology and Life Sciences
• language: English
• id: 9150844
• date added to LUP: 2024-04-22 10:13:27
• date last changed: 2024-04-22 10:13:27