Rhinitis, sinusitis, and upper airway disease
Evolution and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens during the first 2 decades of life

https://doi.org/10.1016/j.jaci.2016.08.014Get rights and content

Background

The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown.

Objectives

We sought to characterize the evolutionary patterns of the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance.

Methods

We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust.

Results

One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA/L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age.

Conclusions

Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.

Section snippets

Study design and population

The MAS, a prospective birth cohort study, recruited a selection of 1314 of 7609 infants born in 1990 on 6 delivery wards in 5 German cities (Berlin, Dusseldorf, Mainz, Freiburg, and Munich).25 The study was approved by local ethics committees. Each parent provided written informed consent at the time of enrollment. All children were followed up at ages 1, 3, 6, 12, 18, and 24 months and then yearly from the age of 3 to 13 years and then at 20 years of age. In this analysis we included subjects

Study population

Overall, 722 of the 1314 subjects recruited in the MAS cohort met the inclusion criteria (see Fig E1 in this article's Online Repository at www.jacionline.org) for this study. We found no difference in parental history of hay fever, number of older siblings, and asthma person-year rates between subjects included and excluded from the study. By contrast, German nationality, higher parental education, longer breast-feeding, mother's nonsmoking status during pregnancy, and MAR were more common in

Discussion

Our study is the first to analyze the evolution of the IgE response to a comprehensive panel of 12 HDM allergens in a longitudinal manner during the first 2 decades of life. In more than 700 German participants followed from birth to age 20 years (the MAS birth cohort study), we found that IgE sensitization to individual HDM allergens increases in prevalence and breadth regarding the number of recognized allergen molecules during the first decade of life. During the first decade of life, the

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    Supported by the Deutsche Forschungsgemeinschaft (DFG) MA-4740/1-1, in part by grants F4602 and F4605 of the Austrian Science Fund (FWF), and by the Christian Doppler Research Association, Vienna, Austria. The Multicenter Allergy Study was funded by grants from the German Federal Ministry of Education and Research (07015633, 07 ALE 27, 01EE9405/5, and 01EE9406) and the German Research Foundation (KE 1462/2-1). D.P. received a DAAD scholarship. O.T. received a Clemens von Pirquet Foundation scholarship.

    Disclosure of potential conflict of interest: C. Lupinek receives payment for lectures form Thermo Fisher Scientific and travel support from the American Academy of Allergy, Asthma & Immunology (AAAAI). R. Valenta receives research support from Austrian Science Fund FWF, Biomay AG, Thermo Fisher Scientific, and Christian Doppler Research Association; serves as a consultant for Biomay AG, Thermo Fisher Scientific, and Fresenius Medical Care; and receives payment for lectures from Thermo Fisher Scientific. P. M. Matricardi serves as a consultant for Thermo Fisher Scientific, HYCOR biomedical, and Euroimmun AG and receives grant support from Thermo Fisher Scientific. The rest of the authors declare that they have no relevant conflicts of interest.

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