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

Abstract

Background: Sensitization in early childhood may precede respiratory allergy in adolescence.

Methods: IgE 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 16years in a population based birth cohort (BAMSE). Symptoms were analyzed by questionnaire at ages 4, 8 and 16years. 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 11years (N=248) and the outcome was studied at 11years.

Findings: In 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 16years (87% and 95%, respectively). The corresponding proportions in the MAAS cohort at 16years were 100% and 100%, respectively, for IgE reactivity to ≥3 of 5 risk molecules.

Interpretations: IgE reactivity to a few allergen molecules early in life identifies children with a high risk of asthma and/or rhinitis at 16years. These findings will be of importance for developing preventive strategies for asthma and rhinitis in children.

Keywords: Asthma; IgE; Prediction; Rhinitis; Sensitisation.

Fig. 1

A. (BAMSE) Flow chart of children in the study base and study population as well as for those remaining for statistical analysis of onset and persistency of asthma, rhinitis and/or eczema at 16 years. Analyses in relation to sensitization to allergen molecules at 4 years with (persistency) and without (onset) children with any of asthma (A), rhinitis (R) or eczema (E) at 4 years. B. (MAAS). Flow chart of children in the study base and study population as well as for those remaining for statistical analysis of onset and persistency of asthma, rhinitis and/or eczema at 16 years. Analyses in relation to sensitization to allergen molecules at 3 years with (persistency) and without (onset) children with any of asthma (A), rhinitis (R) or eczema (E) at 3 years.

Fig. 2

A. (BAMSE). Prevalence of IgE reactivity (%, y-axis) in the population of 786 children at ages 4, 8, 16 years (x-axis) using different sets of molecules at all ages (132), as well as key (18) and risk molecules (4) identified at 4 years. Prevalence indicates IgE reactivity to any of the molecules in each of the three groups. Four risk molecules were identified: Ara h 1 (peanut); Bet v 1 (birch pollen); Fel d 1 (cat) and Phl p 1 (timothy grass pollen). B. (MAAS). Prevalence of IgE reactivity (%, y-axis) in the population of 848 children at ages 3, 5, 8, 11 years (x-axis) using different sets of molecules at all ages (99), as well as key (21) and risk molecules (5) identified at 3 years. Prevalence indicates IgE reactivity to any of the molecules in each of the three groups. Five risk molecules were identified: Der p 1 (Dermatophagoides pteronyssinus); Der f 2 (Dermatophagoides farinae), Phl p 1 and Phl p 5 (timothy grass pollen), and Fel d 1 (cat).

Fig. 3

A. (BAMSE): Probability of rhinitis, asthma or eczema at 16 years in relation to the number of sensitizing risk (green), key (blue) and full panel (red) allergen molecules at 4 years. Probabilities and confidence intervals (hatched lines) were obtained from logistic regression models. Logistic models did not include respiratory allergic disease at 4 or 8 years. B. (MAAS): Probability of rhinitis, asthma or eczema at 11 years in relation to number of sensitizing risk (green), key (blue) and full panel (red) allergen molecules at 3 years. Probabilities and confidence intervals (hatched lines) were obtained from logistic regression models. Logistic models did not include respiratory allergic disease at 3 or 5 years.

Fig. 4

A. (BAMSE) Probability of allergic multimorbidity (asthma and rhinitis) reported at 8 or 16, but not at 4 years of age. B. (MAAS). Probability of allergic multimorbidity (asthma and rhinitis) reported at 8 or 16, but not at 3 or 5 years of age. C. (BAMSE). Probability of having allergic multimorbidity (asthma and rhinitis), i.e. disease at both 8 and 16 years irrespective of disease at 4 years of age. D. (MAAS). Probability of having allergic multimorbidity (asthma and rhinitis), i.e. disease reported at both 8 and 16, irrespective of disease at 3–5 yrs.