Detection of IgE Reactivity to a Handful of Allergen Molecules in Early Childhood Predicts Respiratory Allergy in Adolescence

Abstract

BackgroundSensitization in early childhood may precede respiratory allergy in adolescence.MethodsIgE reactivity against 132 allergen molecules was evaluated using the MeDALL microarray in sera obtained from a random sample of 786 children at the age of 4, 8 and 16 years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16 years. Clinically and independent relevant allergen molecules accounting for ≥ 90% of IgE reactivities in sensitized individuals and at all time-points were identified as risk molecules and used to predict respiratory allergy. The data was replicated in the Manchester Asthma and Allergy Study (MAAS) birth cohort by studying IgE reactivity with the use of a commercial IgE microarray. Sera were obtained from children at the ages of 3, 5, 8 and 11 years (N = 248) and the outcome was studied at 11 years.FindingsIn the BAMSE cohort 4 risk molecules could be identified, i.e.: Ara h 1 (peanut), Bet v 1 (birch), Fel d 1 (cat), Phl p 1 (grass). For MAAS the corresponding number of molecules was 5: Der p 1 (dust mite), Der f 2 (dust mite), Phl p 1 (grass), Phl p 5 (grass), Fel d 1 (cat). In BAMSE, early IgE reactivity to ≥ 3 of 4 allergen molecules at four years predicted incident and persistent asthma and/or rhinitis at 16 years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16 years were 100% and 100%, respectively, for IgE reactivity to ≥ 3 of 5 risk molecules.InterpretationsIgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16 years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.

Early molecular biomarkers predicting the evolution of allergic rhinitis and its comorbidities: A longitudinal multicenter study of a patient cohort

“…sIgE to Bet v 1 is a well‐known qualitative and quantitative marker of OAS . In the Swedish BAMSE cohort study, Bet v 1 was identified as a risk molecule, and as the most prevalent PR‐10 protein, with higher amount of specific IgE . The sensitization to this molecule in early childhood was associated with severe allergic rhinitis to birch pollen at 16 years of age and with OAS .…”

Extract and component‐specific sensitization patterns in Canadian moderate‐to‐severe preschool asthmatics

“…Altogether, these observations support the hypothesis that the skin is a key sensitizing organ both for food and for inhalant allergens that contribute to atopic disease progression. 5 Sensitizations to the latter were less prominent in our cohort, which may reflect regional differences in environmental exposures. Both ED visits and OCS courses were associated with sensitizations to seed storage proteins from peanut and We also observed co-sensitization between allergens of related protein families from different sources, such as for peanut and soy ( Figure S2 ).…”

“…In contrast to other environmental allergens, the association with atopic dermatitis was present for Fel d 1, which may suggest that the skin is an important route of sensitization for this allergen. 5 Sensitizations identified to these allergens as early as 3-4 years old were useful for predicting development of respiratory allergy and asthma up to 16 years of age, in conjunction with environmental allergens from birch, grass, and dust mite. 3,4 To better understand sensitization profiles, component-resolved analysis was performed.…”

Protein Biomarkers in Asthma

“…From epidemiological investigations and birth cohort studies, we know that the development of asthma is preceded by early sensitization followed by clinical symptoms [106][107], often rhinitis, during childhood and may be predicted by measuring IgE reactivity to few allergen molecules [108]. As asthma has early origins and there are differences in its pre-/early-school forms [109], it is crucial to identify biomarkers of IgE sensitization before the clinical manifestation.…”

“…Another important result from recently conducted birth cohort studies is that it seems to be possible to predict the development of allergic respiratory diseases according to "clinically silent" IgE reactivity profiles measured early in the life of children (Fig. 2), which opens possibilities for the prevention of asthma before the onset of symptoms [108,157,158]. Since respiratory allergy and asthma severely affect the life of children, one may consider to initiating preventive medical examinations (i.e., "allergy passport") based on determination of IgE reactivity profiles early in childhood to identify children who may benefit from preventive measures (Fig.…”