Specific IgE-profiles and allergy prediction
Author: Tedner, Sandra G
Date: 2022-10-14
Location: Rolf Luft’s Auditorium, L1:00, Karolinska University Hospital, Solna
Time: 09.00
Department: Inst för kvinnors och barns hälsa / Dept of Women's and Children's Health
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Thesis (1.344Mb)
Abstract
Presence of antibodies of type Immunoglobulin E (IgE-ab), often called sensitization, is common and often precede development of atopic disease, including food allergy. While not all IgE-sensitized individuals develop food allergy, some seem to be at a higher risk. By studying specific IgE-profiles longitudinally in two different birth cohorts we aimed to identify factors associated with atopic disease development and more severe disease.
Firstly, in study I and II, we used the Scandinavian population-based birth cohort PreventADALL, where 2397 infants were randomized into four different groups receiving either preventive skin care with emollient and oil baths from 2 weeks of age, early food introduction (peanut, milk, egg, wheat) from 3 months, both skin/food intervention or control group. In study I the development of IgE in relation to maternal and perinatal factors were studied in 1110 children aged 3 months. We found that 7 % of the infants were sensitized at 3 months of age, mainly against food allergens, but few of them expressed the corresponding molecular allergens. Any positive maternal food sensitization in mid-pregnancy was associated with infant sensitization at 3 months. The aim of study II was to investigate early sensitization to peanut allergen molecules analyzed in children aged 12 months in relation to peanut allergy at 3 years of age. We found that children aged 12 months often were sensitized against peanut extract but few were classified as allergic to peanut at 3 years of age. Children in the food intervention group expressed a different pattern of peanut allergen molecules, with mainly IgE-levels against Ara h 3.
Secondly, in study III and IV we used the Swedish population based BAMSE cohort, consisting of 4089 participants from 6 different parts of Stockholm followed longitudinally between 0-24 years of age. In study III participants were examined longitudinally between age 4-24 years with emphasis on peanut IgE development in relation to symptoms and inflammatory markers such as FENO, blood eosinophils and lung function. Peanut allergy seldom appeared after the age of 8 years and few participants outgrew their allergy in adulthood, those who did all had initially low peanut Ara h 2 IgE-levels. Peanut allergic individuals were found to express higher levels of FENO, blood eosinophils and a more severe asthma. Finally, in study IV we studied sensitization to tree nut extract and tree nut molecular allergens in relation to background factors and symptoms of tree nut allergy at 24 years of age. The tree nut sensitized participants were often asymptomatic, and the majority were birch sensitized. Individuals with storage protein sensitization often had an atopic background, were polysensitized and described more severe allergic reactions.
Conclusion: Sensitization to peanut develop early, and already at 3 months infants express IgE towards peanut while peanut allergen molecule sensitization increased later on. In adolescence peanut allergy tend to remain, especially in participants with early allergies towards other food as well as childhood asthma and atopic dermatitis. Peanut and tree nut storage protein sensitized participants were found to express higher levels of FENO, blood eosinophils and more prone to severe asthma. As few sensitized infants’ express IgE against storage proteins at this age, it could indicate that the IgE development process is not complete at this age, thus still time for a possible tolerance development. Previous studies have indicated that that an early food introduction is preferred over a delayed one, and this research add new insight in this process. It is possible that atopic infants in particular might benefit the most in terms of preventing a more severe allergic phenotype if early food introduction would be applied.
Firstly, in study I and II, we used the Scandinavian population-based birth cohort PreventADALL, where 2397 infants were randomized into four different groups receiving either preventive skin care with emollient and oil baths from 2 weeks of age, early food introduction (peanut, milk, egg, wheat) from 3 months, both skin/food intervention or control group. In study I the development of IgE in relation to maternal and perinatal factors were studied in 1110 children aged 3 months. We found that 7 % of the infants were sensitized at 3 months of age, mainly against food allergens, but few of them expressed the corresponding molecular allergens. Any positive maternal food sensitization in mid-pregnancy was associated with infant sensitization at 3 months. The aim of study II was to investigate early sensitization to peanut allergen molecules analyzed in children aged 12 months in relation to peanut allergy at 3 years of age. We found that children aged 12 months often were sensitized against peanut extract but few were classified as allergic to peanut at 3 years of age. Children in the food intervention group expressed a different pattern of peanut allergen molecules, with mainly IgE-levels against Ara h 3.
Secondly, in study III and IV we used the Swedish population based BAMSE cohort, consisting of 4089 participants from 6 different parts of Stockholm followed longitudinally between 0-24 years of age. In study III participants were examined longitudinally between age 4-24 years with emphasis on peanut IgE development in relation to symptoms and inflammatory markers such as FENO, blood eosinophils and lung function. Peanut allergy seldom appeared after the age of 8 years and few participants outgrew their allergy in adulthood, those who did all had initially low peanut Ara h 2 IgE-levels. Peanut allergic individuals were found to express higher levels of FENO, blood eosinophils and a more severe asthma. Finally, in study IV we studied sensitization to tree nut extract and tree nut molecular allergens in relation to background factors and symptoms of tree nut allergy at 24 years of age. The tree nut sensitized participants were often asymptomatic, and the majority were birch sensitized. Individuals with storage protein sensitization often had an atopic background, were polysensitized and described more severe allergic reactions.
Conclusion: Sensitization to peanut develop early, and already at 3 months infants express IgE towards peanut while peanut allergen molecule sensitization increased later on. In adolescence peanut allergy tend to remain, especially in participants with early allergies towards other food as well as childhood asthma and atopic dermatitis. Peanut and tree nut storage protein sensitized participants were found to express higher levels of FENO, blood eosinophils and more prone to severe asthma. As few sensitized infants’ express IgE against storage proteins at this age, it could indicate that the IgE development process is not complete at this age, thus still time for a possible tolerance development. Previous studies have indicated that that an early food introduction is preferred over a delayed one, and this research add new insight in this process. It is possible that atopic infants in particular might benefit the most in terms of preventing a more severe allergic phenotype if early food introduction would be applied.
List of papers:
I. Tedner SG, Söderhäll C, Konradsen JR, Bains KES, Borres MP, Carlsen KH, Carlsen KCL, Färdig M, Gerdin SW, Gudmundsdóttir HK, Haugen G, Hedlin G, Jonassen CM, Kreyberg I, Mägi CO, Nordhagen LS, Rehbinder EM, Rudi K, Skjerven HO, Staff AC, Vettukattil R, van Hage M, Nordlund B, Asarnoj A. Extract and molecular-based early infant sensitization and associated factors-A PreventADALL study. Allergy. 2021 Sep;76(9):2730-2739.
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II. Tedner SG, Gerdin, SW, Söderhäll C, Konradsen JR, Borres MP, Lie A, Carlsen KCL, Granum B, Haugen G, MD, Hedlin G, Jonassen CM, Mägi CO, Rehbinder EM, Rudi K, Skjerven HO, Staff AC, Vettukattil R, van Hage M, Asarnoj A, Nordlund B. Peanut storage protein sensitization during the first years of life and peanut allergy development– a PreventADALL study. [Manuscript]
III. Tedner SG, Klevebro S, Bergström A, Kull I, Andersson N, Borres MP, Ballardini N, Westman M, Konradsen JR, van Hage M, Nilsson C, Melen E, Asarnoj A. Development of sensitization to peanut and storage proteins over time and relation to markers of airway and systemic inflammation – a 24 year follow up. [Submitted]
IV. Bager J, Tedner SG, Andersson N, Ballardini N, Borres MP, Konradsen JR, Nilsson C, Westman M, Kull I, Bergström A, van Hage M, Melen E, Asarnoj A. Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults. Clin Exp Allergy. 2021 Nov;51(11):1429-1437.
Fulltext (DOI)
Pubmed
View record in Web of Science®
I. Tedner SG, Söderhäll C, Konradsen JR, Bains KES, Borres MP, Carlsen KH, Carlsen KCL, Färdig M, Gerdin SW, Gudmundsdóttir HK, Haugen G, Hedlin G, Jonassen CM, Kreyberg I, Mägi CO, Nordhagen LS, Rehbinder EM, Rudi K, Skjerven HO, Staff AC, Vettukattil R, van Hage M, Nordlund B, Asarnoj A. Extract and molecular-based early infant sensitization and associated factors-A PreventADALL study. Allergy. 2021 Sep;76(9):2730-2739.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Tedner SG, Gerdin, SW, Söderhäll C, Konradsen JR, Borres MP, Lie A, Carlsen KCL, Granum B, Haugen G, MD, Hedlin G, Jonassen CM, Mägi CO, Rehbinder EM, Rudi K, Skjerven HO, Staff AC, Vettukattil R, van Hage M, Asarnoj A, Nordlund B. Peanut storage protein sensitization during the first years of life and peanut allergy development– a PreventADALL study. [Manuscript]
III. Tedner SG, Klevebro S, Bergström A, Kull I, Andersson N, Borres MP, Ballardini N, Westman M, Konradsen JR, van Hage M, Nilsson C, Melen E, Asarnoj A. Development of sensitization to peanut and storage proteins over time and relation to markers of airway and systemic inflammation – a 24 year follow up. [Submitted]
IV. Bager J, Tedner SG, Andersson N, Ballardini N, Borres MP, Konradsen JR, Nilsson C, Westman M, Kull I, Bergström A, van Hage M, Melen E, Asarnoj A. Prevalence and early-life risk factors for tree nut sensitization and allergy in young adults. Clin Exp Allergy. 2021 Nov;51(11):1429-1437.
Fulltext (DOI)
Pubmed
View record in Web of Science®
Institution: Karolinska Institutet
Supervisor: Asarnoj, Anna
Co-supervisor: Söderhäll, Cilla; Nordlund, Björn; Konradsen, Jon
Issue date: 2022-09-22
Rights:
Publication year: 2022
ISBN: 978-91-8016-697-3
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