A document by Magnus Lindqvist. Click on the document to view its contents.

Background Previously identified asthma-susceptibility genes account for a small part of asthma heritability and their role in asthma pathogenesis is unclear. We explored associations between genetic variants in the 17q21 locus, CDHR3 (cadherin-related family member 3) , coding a receptor for Rhinovirus-C, preschool wheeze and asthma at 7 years. Methods Four genetic variants in the 17q21 locus (rs8076131, rs12603332, rs8079416, rs3859192) and rs6967330 in CDHR3 were studied regarding associations with preschool wheeze and asthma at 7 years. We compared 125 cases, enrolled during an acute wheezing episode, with 96 healthy controls at preschool age (6-45 months). At 7 years cases with asthma (N=68) and without asthma (N=31) were compared regarding genetic variants and other clinical parameters. Results Rs8076131 (AA vs GG) was associated with preschool wheeze (OR 3.50, p=0.001), and asthma at 7 years (OR 8.55, p=0.002). Rs12603332 (CC vs TT) was related to asthma at 7 years irrespective of rhinovirus infection at inclusion or current signs of airborne allergy (aOR 7.17, p=0.016). The association of rs6967330 with asthma was restricted to children with specific genotypes in the 17q21 locus; rs8076131-AA (p=0.028) , rs8079416-CC (p=0.006), and rs3859192-TT (p=0.042). Rhinovirus infection at inclusion was significantly related to asthma exclusively in homozygotes rs8079416-CC (p=0.032) and rs3859192-TT (p=0.027). Conclusion Our results highlight the impact of asthma heritability by reporting strong associations between 17q21 locus and asthma in a high-risk cohort. The association of rs6967330 in CDHR3 and early-life rhinovirus infection with asthma at school age might be dependent on specific genotypes in the 17q21 locus.

Aim: The 4th Davos Declaration, convened during the Global Allergy Forum (GAF) in Davos, aimed to elevate patient care for patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. Methods: This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. Results The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. Conclusion: The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to work together to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

Background Allergic rhinitis (AR) is one of the most common chronic diseases worldwide. There are limited prospective long-term data regarding persistency and remission of AR. The objective of this study was to investigate the natural course of pollen-induced AR (pollen-AR) over 20 years, from childhood into early adulthood. Methods Data from 1137 subjects in the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic birth cohort (BAMSE) with a completed questionnaire regarding symptoms, asthma, treatment with allergen immunotherapy (AIT) and results of allergen-specific IgE for inhalant allergens at 4, 8, 16 and 24 years were analysed. Pollen-AR was defined as sneezing, runny, itchy, or blocked nose; and itchy or watery eyes when exposed to birch and/or grass pollen in combination with allergen-specific IgE ≥0.35kU A/l to birch and/or grass. Results Approximately 75% of children with pollen-AR at 4 or 8 years had persistent disease up to 24 years, and 30% developed asthma. The probability of persistency was high already at low levels of pollen-specific IgE. The highest rate of remission from pollen-AR was seen between 16 and 24 years (21.5%), however the majority remained sensitized. This period was also when pollen-specific IgE-levels stopped increasing and the average estimated annual incidence of pollen-AR decreased from 1.5% to 0.8% per year. Conclusion Children with pollen-AR are at high risk of persistent disease for at least 20 years. Childhood up to adolescence seems to be the most dynamic period of AR progression. Our findings underline the close cross-sectional and longitudinal relationship between sensitization, AR, and asthma.

Background: Respiratory birch pollen allergy and associated oral allergy syndrome affect more than 150 million people. IgE cross-sensitization to major birch pollen allergen Bet v 1 and pathogenesis-related (PR10) plant food allergens is responsible for the pollen-food allergy syndrome. Methods: We designed a recombinant protein, AB-PreS, consisting of non-allergenic peptides derived from the IgE binding sites of Bet v 1 and the cross-reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB-PreS was expressed in E. coli and purified by chromatography. The allergenic activity of AB-PreS was tested using sera and basophils from birch pollen patients allergic. The protective effect of AB-PreS was assessed by inhibition ELISA test using sera allergic patients and from immunized rabbits. Results: IgE-binding experiments and basophil activation test revealed the hypoallergenic nature of AB-PreS. IgG antibodies induced by 5 injections with AB-PreS inhibited allergic patients’ IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract-based vaccines. Additionally, immunization with AB-PreS induced HBV-specific antibodies potentially protecting the infection. Conclusion: The recombinant AB-PreS-based vaccine is hypoallergenic, safe and superior to currently registered allergen extract-based vaccines for the treatment of the birch pollen food allergy syndrome.

Background: Exhaled nitric oxide and blood eosinophils are clinical asthma type 2 markers in use. Immunoglobulin E (IgE) is often involved in the inflammation associated with atopic asthma. The effect of both blood eosinophils and allergen-specific IgE on exhaled nitric oxide levels is not completely understood. Twin-design studies can improve understanding of the underlying contribution of genetically and/or environmentally driven inflammation markers in asthma. Our aim was to disentangle the covariance between asthma and exhaled nitric oxide into genetic and environmental contributions that can account for inflammation markers in a paediatric population. Methods: This population-based, cross-sectional twin study enrolled 612 monozygotic (MZ) and same-sex dizygotic (DZ) schoolchildren. Multivariate structural equation modelling was utilized to separate the covariance between asthma and exhaled nitric oxide into genetic and/or environmental effects, taking allergen-specific IgE level and blood eosinophil count into account while controlling for confounding factors. Results: The cross-twin/cross-trait correlations had a higher magnitude in the MZ twins than in the DZ twins indicating that genes affect the association. The likelihood ratio test for model fitting resulted in the AE model as the most parsimonious. A majority, 73%, of the phenotypic correlation between asthma and exhaled nitric oxide, r=0.19 (0.05–0.33), was attributable to genetic effects which mainly was due to the allergen-specific IgE level. Conclusions: This study indicate that the association between asthma - exhaled nitric oxide in children is to a large extent explained by genetics via allergen-specific IgE-level but not blood eosinophils. This might partly explain the clinical heterogeneity in this group. A next step could be to include allergen-specific IgE level in multivariate omic-studies.